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GUTHRIE McCONNELL, M- D. 



Pathology 

i2mo of 523 pages, illustrated 

Second Edition 
Flexible leather, $2.50 net 



Pathology and Bacteriology for 
Dental Students 

i2mo of 309 pages, illustrated 
Just Issued 



PATHOLOGY AND 
BACTERIOLOGY 

FOR DENTAL STUDENTS 



BY 

GUTHRIE McCONNELL, M. D. 

Assistant Surgeon, Medical Reserve Corps, U. S. N.; formerly Pro- 
fessor of Pathology and Bacteriology in the Philadelphia Dental Col- 
lege and in the Medical Department, Temple University; formerly 
Demonstrator of Pathology, Medico-Chirurgical College of Philadel- 
phia; formerly Assistant Demonstrator of Histology, University of 
Pennsylvania, etc. 



ILLUSTRATED 



PHILADELPHIA AND LONDON 

W. B. SAUNDERS COMPANY 

1915 



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<f> 



* 



% 



Copyright, 1915, by W. B. Saunders Company 



PRINTED IN AMERICA 



PRESS OF 

. B. 8AUNDERS COMPANY 

PHILADELPHIA 

MAR IChji5 
©CI.A393924 



(fileO O 



PREFACE 



Important as pathology and bacteriology are in the study 
of dentistry, there are certain facts that must be considered. 
Such students deal with a distinctly limited portion of the 
great extent of the above subjects, and consequently should 
not be expected to become specialists in them. Yet a thorough 
drilling in the underlying groundwork is essential. 

It has become evident, therefore, as a result of several years 
of teaching, that the text-books as prepared for medical 
students contain much that can well be omitted from the den- 
tal curriculum. For that reason this manual has been pre- 
pared. One that is expected to contain a full presentation of 
general pathology and bacteriology and what additional along 
special lines as has been considered advisable. With a com- 
plete knowledge of the basic principles of these subjects, the 
student will then be able to apply them to his work, and later, 
if he so desires, to specialize. It is hoped that this volume 
will be found to accomplish the end desired. 

Guthrie McConnell. 
Philadelphia, Pa. 
February, 1915. 



ri 



CONTENTS 

CHAPTER I page 

Pathology 17 

CHAPTER II 

Disorders of Metabolism 22 

CHAPTER III 

Circulatory Disorders 35 

Hyperemia 37 

Hemorrhage 39 

Thrombosis 43 

Embolism 46 

Edema or Dropsy 5° 

Interstitial Emphysema 5 1 

CHAPTER IV 

Retrogressive Processes 52 

Atrophy 52 

Degenerations 53 

CHAPTER V 

Cell Division 75 

CHAPTER VI 

Inflammation and Regeneration 82 

CHAPTER VII 

The Specific Inflammations (Granulomata) 96 

Tuberculosis 96 

Leprosy 99 

Glanders 102 

Sporotrichosis 104 

Actinomycosis 104 

Mycetoma 106 

Syphilis 107 

CHAPTER VIII 

Progressive Tissue Changes ; 112 

Hypertrophy 112 

13 



14 CONTENTS 

CHAPTER IX page 

Tumors or Neoplasms. 115 

Tumors of Embryonal Connective Tissue 125 

Sarcoma 125 

Tumors of Adult Connective Tissue 134 

Fibroma 134 

Myxoma 135 

Lipoma , 135 

Chondroma 137 

Osteoma 137 

Myoma 139 

Neuroma 139 

Hemangioma 140 

Lymphangioma 141 

Odontoma 141 

Dental Cysts 148 

Tumors of Epithelial Tissues 149 

Papilloma 149 

Adenoma 150 

Hypernephroma 152 

Glioma 153 

Carcinoma 153 

Squamous Epithelioma 157 

X-ray Carcinoma; Rodent Ulcer 158 

Adenocarcinoma 159 

Chorio-epithelioma 163 

Placental Mole; Hydatid Mole 163 

Chorio-epithelioma Malignum 164 

Teratoma 164 

Dermoid Cysts; Ovarian Dermoids 164 

Sporadic Teratoma 165 

Cysts 166 

CHAPTER X 

Special Pathology of the Mouth 167 

The Tonsils 174 

The Pharynx 177 

The Salivary Glands 1 79 

CHAPTER XI 

Bacteria 181 

The Yeasts 181 

The Molds 182 

The Higher Bacteria 182 

Classification of Bacteria 183 

Growth of Bacteria 188 

Products of Bacterial Growth 190 

CHAPTER XII 

Sterilization and Disinfection 192 



CONTENTS 15 

CHAPTER XIII p AGE 

Bacteriologic Methods 199 

Culture-media 199 

Examining Bacteria 205 

Staining Bacteria 205 

Methods for Staining Spores 209 

Staining of Flagella 210 

CHAPTER XIV 

Specific Micro-organisms 211 

Organisms of Suppuration 211 

CHAPTER XV 

Infection 252 

The Cardinal Conditions of Infection 257 

Immunity 259 

CHAPTER XVI 

Laboratory Technic 275 

Examination of Fresh Material 275 

Decalcification 280 

Injection 282 

Embedding Methods 282 

Cutting Sections 286 

Staining * 287 

Nuclear Stains 288 

Diffuse and Double Staining 293 

Elastic Fiber Stain 295 

Blood Staining 297 



Index. 



299 



PATHOLOGY and BACTERIOLOGY 
FOR DENTAL STUDENTS 



CHAPTER I 
PATHOLOGY 



"Pathology is that subdivision of biology which has for 
its object the study of life in its abnormal relations." It 
is the science that treats of disease in all its aspects. 

By "disease" is meant any condition in which there is a varia- 
tion from the normal aspect of the organism; it may be either 
a structural or a functional deviation. 

Pathology also may be subdivided into two sections: one 
known as morbid anatomy and histology, in which the lesions 
are structural. The other, morbid physiology, in which the 
changes are functional. 

The main heading may be again subdivided into general 
pathology, that deals _with abnormal processes common to the 
entire organism, such as inflammation, fever, etc., and special 
pathology, that includes the changes within special organs. 

Under etiology are considered the conditions giving rise 
to disease. They may be either predisposing or exciting. 

Predisposing causes are those that in any way lower the 
vitality of the individual and thus render him more suscep- 
tible; such as bad hygienic surroundings, poor food, bad air, 
noxious gases, fatigue, extremes of temperature, drugs, injury, 
pre-existing disease. 

Exciting causes include mechanical forces, sudden extremes 
of heat and cold, electricity, poisons, parasites, and also certain 
mechanical abnormalities, such as defects in the heart- valves. 



1 8 PATHOLOGY 

Although the causes are divided into these two classes, a 
predisposing cause if acting with great severity may readily 
excite disease. 

The individual may be the seat of two diseases, one acting 
primarily and another following secondarily. 

The latter may be either the direct result of the primary 
or may have nothing whatever to do with it. Infection of 
the lung by the tubercle bacillus gives rise to phthisis; later 
on there may be involvement of pleura or of intestines, or a 
person suffering from chronic nephritis will often die from 
a secondary pneumonia. 

Traumatism may cause disturbances of function more or 
less marked according to the extent, severity, rapidity, and 
duration of its action. 

If it takes the form of constant pressure, there will be mal- 
nutrition and atrophy of the part on account of the inter- 
ference with the blood-supply. If the pressure is intermit- 
tent, hyperemia may occur and hypertrophy take place. 

When the force is sudden the lesions vary according to the 
instrument used. If sharp, there are lacerations; if dull, con- 
tusions. 

According to the locality, there may be fractures and con- 
cussion. In all these injuries there is greater or less destruc- 
tion of tissue, followed by the phenomena of inflammation, 
with either recovery or death. 

Temperature. — Following the local action of extreme heat 
a condition known as a burn results, in which there is relax- 
ation of the blood-vessels, exudation of serum, and possibly of 
blood. The extent of the injury to the tissues depends on the 
degree of heat and its time of action. According to the extent, 
burns may be divided into four classes: (i) Hyperemia of the 
exposed surface; (2) extravasation of serum and liquefaction 
of certain cells, thus forming vesicles; (3) coagulation of the 
cellular protoplasm with resulting necrosis and extension into 
the deeper tissues; (4) charring of the tissues and extensive, 
deep involvement. 

Death may result from burns, either immediately from 
shock or later from exhaustion, from a perforating ulcer of 



X-RAYS 19 

the duodenum, or from toxic substances formed either within 
the body or absorbed from the skin. There may be marked 
alterations within the blood and their action may prevent the 
kidneys from carrying on their functions. 

The cause of the duodenal ulcer is not clear, but may de- 
pend upon thrombosis of some small vessel and subsequent 
digestion by the gastric juice. As a rule, a burn, even of the 
first degree, will prove fatal if it involves one- third the surface 
of the body. 

If the exposure has been general, the result will vary accord- 
ing to the cause, whether steam, dry air, or sun, etc. Expo- 
sure to dry air or sun may cause heatstroke or heat exhaus- 
tion. In the first there occur symptoms of heart failure, 
dyspnea, and coma, if severe. Usually the pulse is full and 
rapid, face flushed, very high temperature, dry skin, labored 
breathing, unconsciousness, and muscular relaxation. In heat 
exhaustion the skin is moist, cool, pale, pulse small and 
soft, unconsciousness unusual, and temperature may be sub- 
normal. 

Extreme cold ' will bring about conditions very similar to 
those resulting from heat, and will have various symptoms, 
according to whether the effects have been superficial or deep. 
In the former the tissue may completely recover, but in the 
latter the blood-vessels may be involved and gangrene follow. 

The primary effect of cold is to bring about a contraction 
of the superficial blood-vessels. This, however, gives way 
to a paralytic dilatation, on account of which more blood 
enters the chilled part and the entire body will be affected. 

If the tissue should freeze during the stage of contraction, 
the part would appear pale; if during that of dilatation^ it 
would be swollen and dusky in color. 

Electricity causes destruction of tissue either by the heat 
generated or by the resistance of the body to its passage. 

Death may result instantly from disturbance of the ner- 
vous system or there may be extensive and destructive burns. 
Sometimes there is involvement of internal organs. 

A'-rays when applied too closely or for too great a length of 
time occasionally give rise to a dermatitis or even to burns 



20 PATHOLOGY 

of the first, second, or third degrees. As a sequel to the 
dermatitis, squamous-celled carcinoma has quite frequently 
developed and gone on to a fatal termination. 

Barometric pressure may cause disturbances if it be either 
greatly increased, as in deep-sea divers or caisson- workers, 
or diminished, as in mountain-climbers and in persons ascend- 
ing in balloons. In the latter the blood shows an increase 
in the number of red corpuscles, in their specific gravity, and 
in their hemoglobin content. 

Season also has a distinct effect upon disease; pneumonia 
and bronchitis being most common in winter, typhoid fever 
and malaria in spring, yellow fever and enteric disorders in 
the summer. In cold weather certain diseases become more 
frequent on account of the crowding of the people. 

Intoxication. — A poison is a substance which when intro- 
duced into the living body in a relatively small amount will 
disturb the structure or functional activity. These substances 
may be formed within the body through faulty metabolism 
and give rise to endogenous or auto-intoxication. They may 
result also from faulty elimination, irregular absorption, in- 
complete chemical transportation, or excessive glandular secre- 
tion. They may be introduced from without, exogenous in- 
toxication. The exogenous may be (i) immediate and indis- 
criminate in their action or they may be (2) remote and selective. 

1. The first group includes the caustics and irritants. Their 
effects are the more marked the ^greater the concentration, 
and may be purely local. The poison may, however, be ab- 
sorbed and give rise to remote effects. In this class belong 
the salts of the heavy metals, a few vegetable substances, 
and some animal products. 

The effects may vary from a slight reddening to marked 
necrosis and sloughing. They are brought about by abstract- 
ing the water from the tissue, by coagulating the albumins, 
and forming definite compounds with the elements. The 
effect depends on various conditions both of the individual 
and of the poison. If a patient has been addicted to the use 
of a drug, a dose fatal to others may cause in him very slight 
disturbance, a condition known as tolerance, and not similar 



ANIMAL PARASITES 21 

to immunity. Sometimes a very large dose may cause vomit- 
ing, and the poison is in that way removed. 

2. Many of the first group come secondarily into this class 
by being absorbed and taken up into the blood. They may 
unite with the hemoglobin or they may bring about hemolysis, 
a destruction of the red corpuscles. 

When the poison combines with the hemoglobin, forming 
methemoglobin, the union is so close that the oxygen can no 
longer be taken up and supplied to the tissue. Death then 
results from a general asphyxia. Instead of death, cyanosis 
may develop, this commonly resulting from the use of coal- 
tar products. 

Strychnin is selective in its action, in that it stimulates the 
respiratory centers and the motor nerves. Bromids depress 
them. 

Foreign bodies that are not living may cause disease by 
mechanically interfering with the functions of the body. The 
most important causes of disease are, however, bacteria, the 
lowest forms of vegetable life. They are almost ubiquitous 
and give rise to many disturbances of function. It is not, 
however, always possible to prove the relationship between 
bacteria and disease. Koch has advanced four laws. They 
are: (i) The bacteria must be found in the diseased individual; 
(2) they must be capable of cultivation upon media outside the 
body; (3) pure cultures introduced into a healthy animal must 
produce the disease in the animal; (4) the bacteria must be 
recovered from the inoculated animal. 

Diseases caused by bacteria are capable of transmission 
from a person to person and are generally termed infectious. 
They may gain entrance into the body through abrasions of 
the skin and mucous membranes, through the air or by means 
of the digestive tract, through the genito-urinary tract, or 
they may be transferred from the maternal to the fetal blood 
in the uterus. 

Animal parasites may frequently be the cause of disease. 
To this class belong the various intestinal worms and cer- 
tain blood organisms, as the plasmodium of malaria, the filaria, 
the trypanosomes, etc. 



CHAPTER II 

DISORDERS OF METABOLISM 

By metabolism is meant those physiologic processes brought 
about in living tissue by means of which the individual is 
able to form new tissue and reintegrate the old. Under this 
head comes the rejection of those substances that are unfit 
for use in the bodily economy. 

In order that the functions of the body be carried on in a 
normal manner it is necessary that the amount taken up by 
the cells must balance the output. The metabolic equilibrium 
must be maintained. To carry on the work it is not sufficient 
that new material be taken in, more is required. These new 
substances must be assimilated by the body, broken down into 
various parts, and the waste portions excreted. Disturbances 
of any of these above factors, constituting metabolism, may 
give rise to diseased conditions of varying importance. 

When the tissues are unable to carry on these molecular 
exchanges a pathologic condition exists. This may be either 
functional or structural, the latter generally being secondary 
to the former. 

Metabolism may be divided into two classes, according to 
whether simple substances are built up into complex, or the 
complex broken down into the simple. The building-up or 
constructive variety is called anabolic metabolism; the break- 
ing down or destructive, catabolic metabolism. 

By means of catabolism the "end products," those sub- 
stances not required by the body, are formed, such as urea, 
water, etc. Anabolism is concerned in the rearranging of 
molecules so as to render them suitable for food. 

A food is a substance that will form new or reintegrate old 
tissues. It may be either in excess or in diminution, or may 



METABOLISM 23 

vary in quality, the amount required depending upon the 
activity of the individual. 

The assimilation of food depends upon the presence within 
the gastro-intestinal tract of certain digestive ferments, which 
may vary greatly in quantity. 

The protein substances are acted upon by the pepsin in the 
stomach and the trypsin from the pancreas. Pepsin acts in 
an acid medium; trypsin, in an alkaline. The necessary acid 
in the stomach is the hydrochloric. Changes from the nor- 
mal amount of pepsin are unusual, but there may be great 
variations as far as the acid is concerned. It may be increased, 
hyperchlorhydria; diminished, hypochlorhydria; or absent, achlor- 
hydria. If absent or much diminished, the food, not being 
properly digested, will undergo fermentation. If there be any 
obstruction at the pylorus the stomach will tend to dilate. 

The carbohydrates are acted upon first in the mouth by the 
salivary ferment, ptyalin; then in the intestines by amylopsin, 
a ferment derived from the pancreas. 

The fats are acted upon by steapsin, a pancreatic ferment, 
and by the bile. 

The condition of the individual depends upon the assimila- 
tion of the food, which may be abnormal in quantity or 
quality. 

If the quantity taken up by the individual is diminished, 
either by lack in amount or by being deflected from its proper 
channels, certain pathologic conditions will result. These 
may be emaciation or starvation, in which case the body weight 
diminishes, the temperature falls, and the energies all fail. 
At first the reserved food is called upon. The circulating 
proteins are first used up, then the glycogen, and afterward 
the fats and the muscles. The heart and the central nervous 
system are the last structures to be involved. The organs 
become smaller, the excretions and secretions are gradually 
suspended. In the blood the leukocytes become much fewer, 
although the red cells appear in normal number. This is 
probably due to the loss of the blood-serum. Death takes 
place slowly, either from exhaustion, disorders of metabolism, 
or by terminal infections. 



24 DISORDERS OF METABOLISM 

In marasmus, a term applied to babies and old people, the 
wasting away takes place more slowly than in starvation. 
In it the trouble is very frequently not due to lack in quantity 
of food, but to improper assimilation. 

If during the course of a definite disease these symptoms of 
slow starvation appear, the condition is called cachexia. In it 
there is a peculiar yellowish color of the skin and also a marked 
anemia. It is probably due to the formation of toxic sub- 
stances, many resembling ferments, which produce injurious 
effects upon the normal tissues of the body. 

Rickets, or rachitis, is a condition of childhood that is indi- 
cated by structural changes of the bones, particularly those 
of the pelvis and of the lower extremities. It is characterized 
by an excessive formation of cartilaginous bone followed by a 
deficient deposit of bony salts. Such bones are not perfectly 
rigid and tend to show more or less deformities on that ac- 
count. Eventually enough salts may be deposited to render 
the bone rigid, but it will retain its irregular structure. In 
these children dentition is late and the teeth readily undergo 
carious changes. 

If larger amounts of food are taken than are necessary for 
the bodily requirements, the excess will be carried through 
the intestines unacted upon. It may result in an excessive 
formation of fatty tissue, giving rise to the condition known as 
obesity or polysarcia. This is due either to the excessive ab- 
sorption of food, either fats or substances, like carbohydrates, 
whose catabolism yields fats, or to inadequate combustion of the 
fats so acquired. In some cases both factors may play a part. 

In asphyxia there is a lack in the amount of oxygen and 
an increase in the carbon dioxid. In this process there is 
first a period of increase in the inspiratory efforts, then in the 
expiratory, and finally exhaustion. After death the heart, 
particularly the right side, is found to be distended with blood. 

Dyspnea is a slight lack of oxygen, sufficient to stimulate 
but not to depress the respiratory centers. Cyanosis, a bluish 
color of the skin, particularly of the face, then appearing. 
Apnea is a condition in which there is a period when no respira- 
tory action takes place. 



CRETINISM 25 

Abnormalities in the secretions of the organs may cause 
marked disturbance. The secretions may be either internal 
or external. The external pass directly from the glands by 
means of ducts. The internal pass slowly into the blood, 
which carries them to all parts of the body. In addition to the 
actions of the better known internal secretions are others, 
called hormones, w T hose functions appear to be to stimulate to 
full activity other digestive glands, even those situated at a 
distance. 

The thyroid secretion, when lessened or absent, gives rise 
to the condition known as myxedema. In this the skin be- 
comes much swollen and firm, particularly in the region of 
the face. The skin will not pit on pressure nor are the depend- 
ent portions affected. The hair frequently falls out, the voice 
undergoes changes, and there are commonly decided dis- 
turbances of mentality. If sheep's thyroid gland is given in 
such cases there is frequently a decided improvement. 

Cretinism is a very similar but more severe condition result- 
ing from disease of the thyroid during intra-uterine life or 
in early childhood, usually appearing during the first year. 
The child does not develop, remains a dwarf, there is more 
or less complete loss of mind, the lips are very thick, tongue 
large, and the abdomen very pendulous. Frequently several 
members of a family are found to be suffering from it. The 
state is also occasionally markedly hereditary. 

If the thyroid secretion be increased, there may result ex- 
ophthalmic goiter, or Basedow's disease. It is characterized 
by enlargement of the thyroid gland, paroxysms of palpitation 
of the heart, bulging of the eyes, and nervous excitement. 
In this the administration of sheep's thyroid increases the 
symptoms. 

The relationship between the thyroid gland and general 
disease is not clearly understood. There appears to be dis- 
tinct bearing upon the nervous system and also upon the meta- 
bolic processes taking place within the body. The active prin- 
ciple seems to be "thyroidin," a substance that contains nearly 
10 per cent, of iodin. 

The parathyroids are several small pea-like bodies situated 



26 DISORDERS OF METABOLISM 

close to the thyroid, and histologically resemble the unde- 
veloped thyroid. Their removal is followed by the condition 
called tetany, which manifests itself by exophthalmos, rapid 
respiration, and painful tonic muscular spasms, most marked 
in the hands and feet. These symptoms may be due to a loss 
of ability to neutralize toxins. Relief from them has been ob- 
tained by the intravascular use of a soluble lime salt. 

The secretion of the adrenals is obtained from the medullary 
portion which is developed from the same source as the sympa- 
thetic ganglia. It is evidently derived from the chromaffin 
cells, so-called on account of their affinity for the chrome salts. 
Wherever those cells are present the active principle can be 
procured, the greatest collection being in the adrenal. This 
secretion is evidently of marked importance, as disease of or 
removal of those bodies causes severe disturbances in the indi- 
vidual. If completely removed, collapse and death occur 
within a few hours. When the breaking down has taken place 
slowly, a condition known as Addison's disease results. In it 
there is an increasing weakness, accompanied by anemia, emacia- 
tion, and a peculiar bronzing of the skin and mucous membrane 
of the mouth. 

Whether or not it has a relation to the pigmentation of the 
skin and to the cachexia is not settled, but it is probably the 
result of oxidation by the secretion. 

The action of the adrenal secretion seems to be more upon 
the vasomotor system. When applied locally the vessels will 
contract, and if injected into the circulation will cause a rise in 
blood-pressure. This is due to the contraction of the arterioles. 

The secretion of the pituitary body seems to bear definitely 
upon the nutrition of the tissues. When diseased the condi- 
tion of acromegaly is generally present. In it there is a marked 
enlargement of the bones of the face and of the extremities. 
The enlargement is due to an actual hypertrophy of the parts 
involved. Accompanying this there is usually some interfer- 
ence with speech, and the memory is slightly affected. 

In the pancreas, besides the three external secretions, there 
is also an internal one. It seems to be chiefly concerned in 
carbohydrate metabolism; it is a glycolytic ferment. 



MILD DIABETES 27 

Diabetes is a disease in which the carbohydrates are not 
properly assimilated, and is characterized by the persistent ap- 
pearance of sugar, chiefly as dextrose, in the urine. In this 
way it differs from alimentary glycosuria, in which the sugar 
appears transitorily. The abnormal condition of the urine 
in diabetes is the direct result of an altered composition of the 
blood, which in turn is caused by changes in metabolism. Ex- 
amination of the blood in diabetes always shows an increase 
of sugar above the normal of 0.1 per cent., a condition known 
as hyperglycemia. This increase of sugar may be due to any 
of the following conditions: (1) Impairment of the glycogenic 
function of the liver and muscles, caused by the cells being 
unable to store dextrose as glycogen ; (2) impairment of the power 
of the muscles and other tissues to utilize dextrose; (3) over- 
production of dextrose from glycogen, protein, or fat. 

As the pathology of many cases of diabetes is so uncertain 
or obscure, it is difficult to classify them according to the 
pathologic conditions, but from the point of view of metabolism 
diabetic patients may be divided into two great groups: (1) Cases 
of mild diabetes, in which the glycosuria ceases as soon as the 
carbohydrates in their food have been sufficiently reduced. 
In most of these cases the glycosuria depends entirely upon the 
quantity or kind of carbohydrate in the food. (2) Cases of 
severe diabetes, in which the glycosuria does not cease as 
soon as their diet is freed from carbohydrates. They must, 
therefore, excrete dextrose derived from protein or fat as well 
as from carbohydrates. 

Mild Diabetes. — This group may be divided into four varie- 
ties, according to the pathologic condition which causes the 
change in metabolism: 

1 . Neurogenous diabetes is caused by the action of the nervous 
system upon the liver. It has been shown that puncture at 
the tip of the calamus scriptorius in the fourth ventricle is fol- 
lowed generally by hyperglycemia and glycosuria. At present 
it would appear that this hyperglycemia following puncture is 
due to dextrose produced from hepatic glycogen, and that this 
conversion is an overproduction because it takes place irrespec- 
tively of the needs of the tissues. A similar condition may 



28 DISORDERS OF METABOLISM 

occur in the course of tumors or diseases of the brain, as well 
as in fractures at the base of the skull. 

2. Hepatogenous Diabetes. — In view of the importance of 
the glycogenic function of the liver in preventing hyperglycemia 
after carbohydrate meals, it is not surprising that parenchy- 
matous disease of the liver may produce glycosuria. 

3. Lipogenous Diabetes. — Patients suffering from any variety 
of mild diabetes may be fat, but there appear to be cases in 
which the diabetes has some direct connection, at any rate in 
point of time, with obesity. It has been suggested that there 
are patients who have lost the power of assimilating carbo- 
hydrates properly, but who do not have glycosuria as long as 
they retain the power of converting the excess of carbohydrates 
into fat. When this power becomes impaired, these patients 
develop glycosuria. 

4. Pancreatic Diabetes. — In this variety there is a partial 
failure of the internal secretion of the pancreas which induces 
a mild degree of diabetes. Although this form of diabetes is 
pathologically distinct, clinically there is nothing to distinguish 
it from the other varieties considered. It has, however, been 
found that if the lesion progresses sufficiently the diabetes 
changes from the mild to the severe type, and of no other 
variety of mild diabetes does this hold true. 

Severe Diabetes. — The essential feature in the metabolism 
of these cases is that they excrete dextrose derived not only 
from carbohydrate food, but also either from tissue fat or from 
protein food, or from both sources at the same time. This dis- 
turbed metabolism is evidently due to the absence of an in- 
ternal secretion of the pancreas. Tying the pancreatic duct 
does not cause glycosuria, but extirpation of the organ gives 
rise to a glycosuria closely resembling diabetes and terminat- 
ing fatally. 

The structures most intimately concerned are the islands 
of Langerhans which are most numerous in the tail or splenic 
end of the gland, and are supposed to regulate the metabolism 
of sugar. If the lesions involve these structures, then diabetes 
ensues; if, however, the head end alone is affected, there may be 
no glycosuria. The common lesion of the islands is primarily 



UREMIA 29 

a connective-tissue overgrowth which frequently undergoes a 
degeneration belonging to the hyaline type. There is the forma- 
tion of a homogeneous substance that stains with the acid dyes, 
but does not give the amyloid reaction. 

The natural termination of all severe and progressive cases of 
diabetes is in coma due to the formation of acetone bodies, the 
mother substance of which is beta-oxybutyric acid. This on 
oxidation yields ace to-acetic acid, and this in turn, by the loss 
of C0 2 , forms acetone. The main source of these acetone 
bodies is probably fat and not proteins, but it is quite possible 
that they do have a double source of origin, and that the rela- 
tive quantities derived from the two sources will vary with 
circumstances. 

According to the quantity and kind of acetone body ex- 
creted on a standard diet containing about 50 to 70 gm. of 
starch, it is possible to divide severe diabetes into three stages: 
In the first stage are those which secrete acetone alone, and in 
quantities which vary from the normal 0.05 to 0.5 gm. a day. 
Such cases retain considerable power of utilizing carbohydrates. 
The second stage is marked by the constant appearance of 
diacetic acid in the urine, and this always takes place when the 
excretion of acetone is more than about 0.5 gm. a day. Patients 
in this stage still retain some power of utilizing carbohydrates. 
The third stage begins when beta-oxybutyric acid is always 
present in the urine, and this is so when more than about 1 gm. 
of acetone is excreted in the day. Cases in this stage show 
little or no power of utilizing carbohydrates. 

The coma that results is probably due to changes taking 
place within the cells of the body and not in the blood, the 
hypothesis at present being that the coma is due to a change 
in the reactivity of cells produced by the acidosis. 

Uremia is a condition associated with disease of the kidneys 
and characterized by various clinical manifestations, as drowsi- 
ness, stupor, coma, twitchings of the muscles, cramps, convul- 
sions, vomiting, blindness, and frequently death. The cause 
of this condition is not known. It evidently is not due to an 
increased amount of urea in the blood, as that substance has 
been proved to be but feebly toxic and incapable of producing 



30 DISORDERS OF METABOLISM 

the symptoms of uremia. The evidence indicates the presence 
of poison, either singly or in a group. It may be due to the 
retention within the body of some substance that normally is 
excreted; to the abnormal decomposition in the blood or tissues 
of such a substance, or to the formation of abnormal products. 
Decomposition of urea may result in the production of am- 
monium carbamate and ammonium carbonate, and these sub- 
stances when introduced into the circulation give rise to symp- 
toms resembling those of uremia. Examination, however, of 
the blood in uremia does not show any excess of ammonia. It 
has been suggested that the kidney produces an internal secre- 
tion, and that uremia is due to some change in quantity or 
quality of this theoretic substance. 

Eclampsia is a condition occurring in pregnant women 
that clinically seems closely allied to uremia, although it may 
be present without any albuminuria. When death takes place 
the liver will show congestion, capillary thrombosis, anemic 
and hemorrhagic necroses, and thrombosis. The kidney will 
present a nephritis ranging from a slight parenchymatous de- 
generation to an acute, intense nephritis. It is claimed by 
some that eclampsia is due to a deficient oxidizing capacity 
on the part of the liver which fails to convert protein de- 
rivatives into urea. There are others who believe that the 
toxic substances are probably derived from the fetus or the 
placenta. 

Gout, or podagra, is a disease in which there is deposited 
within the joints, in the articular cartilages, uric acid and its 
compounds. It generally affects the small joints of the hands 
and feet, particularly the big toes. These salts may be de- 
posited elsewhere, as tophi in the cartilages of the ear and 
in the meninges. As a result of these deposits the joints may 
be much deformed. Lesions of other portions of the body 
are usually present. There is a marked tendency toward 
the formation of connective tissue in the form of interstitial 
nephritis and of arteriosclerosis; fatty changes also take place 
in the heart and liver. Gout usually appears after middle 
life in those who have lived very well, drunk plenty of wine, 
and have not taken exercise. It is a chronic disease, but 



BILE 31 

exhibits periods of acute and painful inflammation lasting sev- 
eral days. 

It is probably the outcome of insufficient oxidation, by which 
the precursors of uric acid and similar bodies are not fully 
oxidized, and by their accumulation and toxicity set up morbid 
changes. 

The salts concerned are the sodium biurates and quadri- 
urates, uric acid existing in the blood in the form of the lat- 
ter. The soluble quadriurates circulating in the blood, if 
in the presence of uric acid and sodium salts in excess, are 
precipitated as insoluble crystalline biurates. 

In oxaluria and phosphaturia there is an excess of either 
oxalic acid salts or of phosphates. The presence of oxalic 
acid is thought by some to be due to the amount present in 
the vegetable matter consumed, while others think it is the 
result of deficient oxidation of the carbohydrates. It is of 
chief importance in the formation of calculi, it being pre- 
cipitated in the crystalline form mainly when there is an in- 
creased amount of calcium in the urine. 

The phosphoric acid exists in the form of the phosphates of 
magnesium, ammonium, and sodium. These may form cal- 
culi in the bladder when they occur in excessive amount in an 
alkaline urine, as they remain in solution if the reaction is acid. 

Acetone and diacetic acid are often found in the blood and 
urine in the later stages of diabetes. 

The bile may vary in amount and consistency and may be 
prevented from passing into the bowel. The normal amount 
secreted varies from 500 to 1000 c.c. in a day. It is com- 
posed chiefly of water, but contains bile salts, cholesterin, 
lecithin, fat, and coloring substances. The salts are the gly- 
cocholate and the taurocholate of sodium. The important 
pigments are bilirubin and biliverdin, both of which are de- 
rived from the blood. Bilirubin undergoes oxidation to form 
various other pigments. It resembles hematoidin, and the 
toxic effects of the retention of bile seem to depend upon its 
presence, as when the bile is freed from its coloring-matters by 
filtration it is only one-third as toxic as in its original con- 
dition. 



32 DISORDERS OF METABOLISM 

The most important function of bile is to increase the activity 
of the pancreatic ferments. It not only increases the fat-dis- 
solving action of the steapsin, but it dissolves and increases the 
solubility of soaps, and so renders their absorption more easy. 
Consequently, if bile is absent from the intestines, but pan- 
creatic juice is still secreted, from one-quarter to one-half of the 
fat taken in the food is unabsorbed. 

Bile is not, as has been supposed, an antiseptic, consequently 
its absence from the intestinal contents neither increases the 
number of bacteria nor their fermentative or putrefactive ac- 
tivity. 

If there should be any obstruction to the outflow of bile 
the condition known as icterus or jaundice follows. This 
obstruction may result from a catarrhal condition or a steno- 
sis of the bile capillaries, inflammation of the common bile- 
duct, or of the papilla. It may be due to foreign substances, 
such as gall-stones, inspissated mucus, round-worms, or tumors 
within the large duct, or to pressure upon it from without. 
The jaundice is due to the absorption of the bile into the gen- 
eral circulation by means of the veins or lymphatics. A large 
amount of it is eliminated by the kidneys, while the excess is 
deposited within the connective tissues. 

As a result of the absorption of the bile the skin is at first 
yellow, but if the condition continues for some time the pig- 
ment oxidizes and becomes greenish in color. This discol- 
oration will be seen in the sclera, the lining of the arterial sys- 
tem, the mucous membranes, and in most secretions and exu- 
dations, normal or pathologic. The heart's action is fre- 
quently slowed (bradycardia) to 50 or even 20 beats a minute. 

The effect upon digestion may be quite marked. There is 
found an excessive amount of fat in the feces. The stools 
become very light in color, due to the absence of hydrobili- 
rubin, and may be very offensive on account of the loss of the 
laxative action of the hepatic secretion and consequent stag- 
nation of the intestinal contents. There may be some inter- 
ference with the outflow of the pancreatic enzyme, which would 
have a distinct effect upon the amount of fat present and also 
upon the color of the feces. 



INTESTINAL DISTURBANCES 33 

Sometimes there are marked nervous symptoms, probably 
the result of the presence of the biliary acids and salts in the 
circulation rather than due to the pigments. 

Another form of jaundice is that of hematogenous origin. 
It occurs when no obstruction to the outflow of bile can be 
found. Although bile cannot be formed in any other place 
than in the liver cells, there are cases in which a general yel- 
lowish discoloration takes place without any hepatic lesion 
being present. It occurs in certain infectious diseases, as in 
yellow fever, malaria, etc., in poisoning by venom and tolu- 
olendiamin, and in the newborn in the form of icterus neona- 
torum. In all these conditions, particularly in the last named, 
there is a very marked destruction of the erythrocytes. The 
blood-pigment is changed into bile-pigment and thus stains 
the tissue. This form may be due to some nervous disturbances 
that cause a contraction of the circular muscles of the bile-ducts. 
It may be that there is an increase in the viscosity of the bile 
on account of the presence of the blood-pigments, and in that 
way the ready outflow is prevented. It has also been shown 
that the concentration of the bile is associated with an inflam- 
matory condition of the bile-ducts. 

Besides the secretion of bile the liver also forms urea and 
glycogen, but these two latter bodies are carried off in the 
blood. 

Intestinal disturbances may bring about a condition of 
putrefaction accompanied by various symptoms of self-intoxi- 
cation, inasmuch as the feces are made up of the remnants of 
digestion and of waste products. Their odor is due to the pres- 
ence of indol and skatol. 

The intestinal disturbances are due chiefly to the presence 
of bacteria and their products. Fermentation may take 
place in the stomach with the formation of acetic, lactici or 
butyric acids, or of alcohol. It results from the breaking 
down of the carbohydrates. In the intestine the proteins 
may undergo putrefaction and produce amido-acids, or aro- 
matic bodies, as acetone,, tyrosin, cresol, skatol, and indol. 
Ptomains may be formed and give rise to many symptoms. 
These bodies resemble quite closely many of the vegetable 



34 DISORDERS OF METABOLISM 

alkaloids and give rise to symptoms similar to those result- 
ing from the drugs. 

As a result of these disturbances diarrhea may occur. In 
this condition the feces are too soft and the bowel movements 
too numerous. It is an attempt to free the body of the irri- 
tating substances and may relieve the patient. The diarrhea 
may be due to increased rapidity of peristalsis, increased 
secretion of the intestines, diminished absorption by the large 
intestine, or disturbances of the controlling nervous mechanism, 
these depending upon many causes. These may be mechanical, 
inflammatory, infectious, obstructive, hepatic, and pancreatic. 

Constipation, or coprostasis, is a condition in which defecation 
may not be sufficiently frequent, the amount of feces insufficient 
or abnormally dry and hard. It may be due to deficient motor 
activity of the colon as a result of weak muscle, deficient reflex 
activity, inhibition of the motor activity, uncontrolled and 
irregular motor activity. It may be due also to excessive force 
required to carry the feces to the pelvic colon. The work to be 
done by the intestinal musculature is excessive whenever the 
bulk or the consistence of the feces offers more than a normal 
degree of resistance, and whenever there is any narrowing of the 
intestinal lumen. 



CHAPTER III 

CIRCULATORY DISORDERS 

The circulation of the blood is maintained chiefly by two 
forces — the rhythmic contraction of the heart muscle and 
the elasticity of the arteries. Other factors concerned are 
the compression of the veins by the muscles and the inspira- 
tory action of the chest. 

As these are the chief factors, any abnormality within them 
will bring about more or less general disturbances of the cir- 
culation. To these may be added alteration in the quantity 
or quality of the blood itself. According as to whether the 
effect is more marked in the systemic or in the pulmonary cir- 
culations the disturbances are more or less widely distributed. 

The circulatory disorders may be cardiac in origin and either 
the result of muscular or valvular lesions. If muscular, there may 
be an excessive or, what is more common, a diminished action. 

The excessive form is seldom lasting, but while present causes 
a rise of blood-pressure, an increased amount of blood within 
the vessels in the part involved, and an increase in the rate of 
flow. If the overaction should be long continued, as a result 
of hard work or by constant stimulation, there would be hyper- 
trophy of the left ventricle. 

Diminished activity is more common and more important 
than the above. It may be brought about in many ways. 
It may be the sequel of a heart muscle weakened by the infec- 
tious fevers or other diseases, by poisons, by lack of nourish- 
ment caused by anemia, or by a blocking of the coronary arteries. 
It may be the result of nervous disturbances with no apparent 
lesion of the muscle, or it may be the result of some valvular 
disorder. 

Sometimes it results from pressure from the outside — that 
exerted by collections of fluid in the pericardium, in the pleurae, 
or by tumors or adhesions. 

35 



36 CIRCULATORY DISORDERS 

As a result of the weakened circulation there is an accumu- 
lation of blood in the venous circulation. If the failure is of 
the left ventricle, there will be a damming back of the blood 
in the left auricle and in the pulmonary circulation. If the 
right heart remains capable, the engorgement will go no fur- 
ther, but when it fails the right auricle becomes distended and 
a condition of general passive congestion ensues. 

In all cases there is a decrease of arterial and an increase 
of venous pressure. 

When the heart's action has become much weakened it 
will be found that the blood tends to gravitate to the more 
dependent portions, giving rise to hypostatic congestion. It 
occurs in the late stages of severe fevers and when death has 
taken place very slowly. The dependent tissues will become 
livid through the accumulation of blood, edematous from 
the escape of fluid from the blood-vessels, and sometimes 
bed-sores may result. A frequent occurrence is a collection 
of blood within the lungs, a condition known as hypostatic 
pneumonia. 

The changes within the arteries may be either organic or 
nervous (vasomotor). Their elasticity may be diminished, 
and their caliber increased or diminished. The alteration 
in caliber may be due to changes within the tissues or to dis- 
turbances of the vasomotor control. 

If there is a paralysis of the controlling nerves, the vessels 
dilate and hyperemia results. On the other hand, stimula- 
tion will cause contraction and subsequent anemia. When 
sufficiently marked, there will be an increase in the blood- 
pressure, interference with the heart's action, and venous 
congestion. 

The most common organic disturbance is a sclerosis of the 
vessel wall, a condition leading to constant interference with the 
arterial circulation. Generally a hypertrophy of the left heart 
follows. If, however, the sclerotic changes are very widely 
distributed, instead of hypertrophy there may be a dilatation, 
on account of the resistance being too great for the heart to 
overcome. 

Changes in the quantity of the blood, either an increase or a 



HYPEREMIA 37 

decrease, are generally only temporary, and soon readjust them- 
selves, either through a contraction or a dilatation of the 
vessels. 

Alterations in the quality have a marked effect upon the 
circulation, probably through the direct action of the toxic 
substances upon the vessel walls or upon the terminal nerve 
filaments. 

Hyperemia. — General Hyperemia. — There may be an in- 
crease throughout the body of the total volume of blood. This 
seldom remains for any length of time, as the various excretory 
structures of the body get rid of it. The condition known 
as plethora is the result of persistent overeating and drinking. 
It is usually associated with a hypertrophy of the left ventricle. 

Local hyperemia is an increase in the amount of blood in 
a part of the body. It may depend upon either an increased 
supply to the part or be due to a diminished outflow — in one 
case a dilatation of the arteries, in the other an obstruction of 
the veins. The first is known as active or arterial, the second, 
as passive or venous, hyperemia. 

Active hyperemia is an excess of arterial blood in a part. 
It occurs with increased functional activity (increased met- 
abolism). It may be brought about through the central 
nervous system or by direct stimulation of the peripheral 
nerves. Any pathologic condition that will bring about a 
local dilatation of the arteries will cause active hyperemia. 

The spinal cord or a nerve may be pressed upon as the result 
of a tumor or of an injury, and a paralytic dilatation occurs. 
The same condition follows the use of certain drugs acting 
peripherally either upon the muscular coat of the artery or 
upon the local nervous mechanism, or both. 

In active hyperemia the part affected is redder than nor- 
mal and more or less swollen as the result of the increased 
amount of arterial blood that it contains. The tempera- 
ture is higher than in the surrounding parts, but never higher 
than that of the internal organs. There is also an increase in 
the rate of the blood-flow. 

This form of hyperemia if continued for some time is fol- 
lowed by (1) hypertrophy of the part on account of the in- 



38 CIRCULATORY DISORDERS 

creased nutrition, (2) parenchymatous degeneration from over- 
nutrition or overstimulation of the cells, and (3) a prolifera- 
tion of the connective tissue around the blood-vessels. 

It is found as one of the phenomena of inflammation. Post- 
mortem, it cannot be recognized on account of the contraction 
of the arterial walls, which drives out the blood. It may persist 
in the kidneys. 



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Fig. 1. — Passive Hyperemia of the Lung. X 250 (Diirck). 
1, Ectatic and distended blood-vessels, filled with blood; 2, engorged 
and tortuous capillaries; 3, lumen of alveolus; 4, increased interlobular 
connective tissue; 5, cells, containing blood-pigment, within the alveolar 
lumen; 6, free, amorphous blood-pigment. 

Passive hyperemia is an excess of venous blood in a part. 
It is the result of a distention of a vein on account of some 
obstruction to the outflow of the blood. This can be caused 
by obstruction within the veins or capillaries, as by thick- 
ening of their walls, by thrombi, or by pressure from without, 
as from a tumor. A common cause for general passive hyper- 
emia is a lesion of the heart-valves. The circulation will 



HEMORRHAGE 39 

continue slowly unless the venous pressure becomes as great 
as the arterial, when it will stop, a condition known as stasis. 

A part the seat of passive hyperemia becomes cyanotic, 
swollen, edematous, cooler than normal, and its function 
less. The rate of blood-flow is lessened. The edema is due 
to the escape of fluid from the blood. If severe, red corpuscles 
may escape. 

Following long-continued passive hyperemia the tissues 
will undergo a fatty degeneration on account of the decreased 
nutrition, or even necrosis and gangrene may result. There 
may also be some increase in the amount of connective tissue. 
Pigmentation from escaped hemoglobin is not uncommon — 
brown atrophy. 

When stasis occurs the blood-corpuscles slowly collect in 
the smaller vessels, the plasma is exuded, and the cells become 
packed closely together. Finally, the outline of the cells can- 
not be seen and the vessels appear to be rilled with coagu- 
lated blood. Such is not the case, as when the circulation 
is re-established the corpuscles separate and move along as 
usual. 

Local anemia or ischemia is the condition in which the part 
contains less than its normal amount of blood. It is most 
commonly due to obstruction by pressure of the flow of arterial 
blood into a part. This may be due to tight bandaging, 
pressure from a tumor, or to thrombi or emboli, or to changes 
in the wall of the vessel. 

Disturbances of the vasomotor system may bring about 
marked lesions. If there is a good collateral circulation the 
area to which the obstructed vessel goes may show very slight 
change. If such is not the case, infarction may follow. An 
anemic area is pale in color, temperature lower, and functional 
activity decreased. 

Hemorrhage is the escape of all the constituents of the 
blood through the walls of the heart or of the blood-vessels. 
It is divided into three classes, according to the vessel from 
which it escapes, as arterial, venous, or capillary. 

It may occur by rhexis, in which case there is a demon- 
strable defect of the vessel wall, or by diapedesis, when there is 



40 CIRCULATORY DISORDERS 

no discoverable lesion. The latter form occurs only from veins 
and capillaries. The method of escape of the corpuscles is not 
clear, but is generally supposed to take place through the stig- 
mata of the lining endothelium. Hemorrhage by rhexis may be 
primary or immediate and secondary or recurrent; the first 
following immediately upon laceration of the vessel wall, the 
second occurring some time after the original injury. 













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Fig. 2. — Multiple Capillary Hemorrhages in the Cerebrum. X 270 

(Durck). 
1, Cerebral substance; 2, engorged capillaries; 3, small artery with 
hemorrhagic infiltration of its walls; 4, hemorrhage by diapedesis in the 
tissues around a small artery; 5, smaller hemorrhagic foci without any 
connection with any blood-vessel visible in the section. 

Hemorrhages may also be designated by special terms ac- 
cording to the area involved. Petechia are minute, circum- 
scribed hemorrhages. Ecchymoses are of moderate extent; are 
what are commonly known as bruises. Extravasations, suffu- 
sions, and sugillations are conditions in which extensive areas 
are implicated. A hematoma is a collection of blood within a 



HEMORRHAGE 4 1 

solid tissue. A hemorrhagic infarct is a circumscribed hemor- 
rhage within tissues, the result of the obstruction of an end- 
artery. 

A hemorrhage may also have a special name according 
to its locality. Cerebral apoplexy is a hemorrhage brought 
about by a rupture of one of the arteries of the brain. According 
to the cavity in which it collects there may be a hemothorax^ 
hemo pericardium, etc. According to its method of escape from 
the body it may be known as epistaxis, bleeding from the nose; 
hemoptysis, from the lungs; hematuria, from the urinary tract, 
etc. 

Hemophilia. — In it no structural changes in the vessel walls 
can be demonstrated, but severe bleeding takes place as the 
result of very slight injuries. In such individuals the hemor- 
rhage resulting from the extraction of a tooth may be very dan- 
gerous and at times fatal. This condition is generally hereditary 
and is transmitted by the mother; as a rule the male children 
manifest the disease, but do not transmit it. On the other hand, 
the females pass it on to the males, but do not themselves mani- 
fest the disease. The most important change, and perhaps the 
only constant one, to be found in the blood in hemophilia is its 
lessened coagulability. This may be due to an excessive devel- 
opment of antithrombin, that substance in the blood which 
prevents coagulation within the vessels under normal conditions. 
It may be, however, that there is a lack of thrombokinase, the 
substance which brings about the coagulation of the blood under 
abnormal conditions. In some bleeders the amount of calcium 
present in the blood is decreased. Hemorrhage in such indi- 
viduals has been successfully treated by the injection of normal 
blood-serum from man or horse. This probably supplies the 
necessary amount of thrombokinase. 

Hemorrhage by rhexis may be caused by: (i) Increased 
blood-pressure, particularly in those cases in which, the blood- 
vessel walls being diseased, their elasticity is diminished. 
(2) Disease of the vessels, in which the walls become so weak 
that they are unable to withstand the normal pressure. (3) 
Traumatism, injury of some form sufficient to cause a lesion 
of the vessel wall. 



42 CIRCULATORY DISORDERS 

Hemorrhage by diapedesis may follow in the course of (i) 
certain diathetic diseases, as scurvy, purpura hemorrhagica, 
leukemia, hemophilia, etc.; (2) in severe inflammations; (2) in 
severe hyperemia, either active or passive; (4) in certain forms 
of poisoning, particularly that by snake-bite; (5) alterations oj 
innervation; (6) in hemophilia. 

Spontaneous arrest of hemorrhage takes place in several ways, 
but depends upon several factors — the direction of the injury, 
whether transverse or parallel to the axis of the vessel; the size 
and nature of the vessel, artery, vein, or capillary; the force of 
the heart's action and the blood-pressure, and the amount of 
fibrin- forming substances present in the blood: (1) When a 
vessel is injured its walls contract and the lumen is diminished 
in size. The vessel also, being elastic, retracts within the sur- 
rounding tissues. (2) The blood, coming in contact with ab- 
normal surroundings, coagulates just outside, then upon, and 
finally within the vessel; this latter being known as a thrombus. 
In this way the vessel becomes plugged and the bleeding ceases. 
Another factor is that, as a result of the escape of large amounts 
of blood, the heart becomes weaker, even to a point where 
syncope may result; following this the blood-pressure falls and is 
unable to displace the clot. 

The results of hemorrhage vary not only according to the 
amount of blood lost, but also as to the rapidity; if occurring 
slowly, the blood-forming tissues have time to supply the loss. 
Then, too, the results depend upon the locality of the hemor- 
rhage, an ounce or so may prove fatal in cerebral apoplexy. If 
the amount has been small, there will be no ill effects ; if compar- 
atively large, weakness and unconsciousness ; if very large, death 
will result from cerebral anemia. When the blood collects within 
the tissue various changes take place. It undergoes coagulation, 
a condition in which fibrin factors acted upon by fibrin ferments, 
in the presence of calcium salts, form a solid body known as 
fibrin. The greater the amount of fibrin, the more difficult is it 
for the tissue to recover. The fluid elements are first taken up 
by absorption by the lymphatics. The corpuscular elements 
and the fibrin break up, hemoglobin is set free, and the particles 
are scattered through the tissue. The greater part will be slowly 



THROMBOSIS 43 

removed by the phagocytes, but some will remain. If the 
coagulation has been extensive the tissues may undergo a lique- 
faction necrosis, giving rise to a cyst. 

Thrombosis is the coagulation of the blood within the vessels 
during life. It may depend upon changes within the blood, 
changes in the cardiovascular structures, and diminution of the 
velocity of the blood-flow. 

The changes of the blood are those which tend to increase 
its coagulability. In the formation of a thrombus there is an 
action of the fibrin ferment or thrombin upon certain of the 
proteins in the blood-plasma. This ferment is not present in the 
normal circulating blood, but is produced after the blood is dis- 
charged from the vessels by the action of tkrombokinase upon 
the thrombogen of the plasma in the presence of calcium salts. 
The thrombokinase is supposed to be liberated by the breaking 
down of leukocytes and blood-platelets. Certain chemical 
and physical substances — alcohol, ether, chloroform, heterolo- 
gous blood-serum — when in the circulation may liberate fibrin 
ferments and thus cause thrombosis. The toxins of pneumonia, 
of diphtheria, and those resulting from extensive burns are 
especially active. 

The lesions of the vessel walls are particularly important. 
Fibrin will be deposited upon the wall of the heart or blood- 
vessels whenever the nutrition of the endothelium of that wall 
is impaired. Diseases leading to the roughening of the endo- 
thelium, particularly arteriosclerosis, are important causes. 
Inflammation of neighboring structures may bring about 
changes within the intima. Ligation of a vessel causes an 
injury to the internal coat, and in that way predisposes to 
coagulation. 

Diminution of the blood-flow may result not only from 
cardiac disturbances, but also from conditions causing a de- 
crease in the lumen of the vessel. As the current slows, the 
leukocytes tend to adhere to the wall of the vessel, blood- 



plates make their appearance, and fibrin is deposited. The 
nutrition of the endothelium suffers, changes take place in 
trie wall, and another factor in thrombosis then arises. The 
appearance of a thrombus depends upon the number of red 



\ 



44 CIRCULATORY DISORDERS 

corpuscles contained within it, and that rests upon the varying 
rapidity of the blood-current at the time of formation. It is 
generally made up of superimposed layers of fibrin. After a 
thrombus has formed there is always a tendency for it to ex- 
tend up the vessel, against the current of the blood, and to 
involve successive branches. 

If the blood were passing through the vessel with consider- 
able velocity, the thrombus would be grayish-white in color, 
and on section would show well-marked lamination. This is 
called a white thrombus. 

If the blood were moving less rapidly, varying numbers of 
red cells would be entangled in the fibrin and the color would 
be brown or grayish red, giving rise to a mixed thrombus. 

If it is formed in a short time from blood that is barely mov- 
ing, a red thrombus will result. 

A true thrombus differs from a postmortem clot within a 
vessel in that the latter is moister, is never adherent to the 
vessel wall, and never laminated. The clot may show also a 
division into pale, "chicken fat," and dark "currant jelly" 
portions as a result of the coagulation taking place after the 
heavier red corpuscles have sunk. 

Thrombi may be classified according to their etiology as: 

i. Infectious — those depending upon the entrance of bac- 
teria into the circulation. 

2. Mechanical — foreign bodies free from organisms. 

According to their period of formation as : 

i. Primary or initial thrombi. 

2. Secondary or consequential, depending upon a pre-existing 
thrombus and usually extending to the first collateral branch 
of the blood-vessel. 

According to their morphology as: 

i. Central, occluding, or obstructing — formed by the coagula- 
tion of the entire mass of blood contained within a certain por- 
tion of the vessel. 

2. Parietal — when attached to the wall of the vessel, but not 
completely obstructing it. 

3. Valvular — parietal thrombi that have become partially 
detached. 



THROMBOSIS 



45 



4. Channeled or tunneled — those in which there still exists 
a lumen through which the blood can pass. May be the result 
of secondary changes in old thrombi. 

5. Ball — thrombi that lie free within the cavities of the 
heart, usually in the auricles. 

6. Polypoid — ball thrombi with pedicles. 







V--- 



„— <? 






X " 




Fig. 3. — Organized and Partly Canalized Thrombus of the Brachial 
Artery. X 32 (Diirck). 
1, Adventitia; 2, tunica media; 3, organized thrombus — i. e., replaced 
by connective tissue; 4, newly formed and in part dilated vessels within 
the thrombus; 5, disintegrated remains of the old thrombus. 



\$feta?nor piloses of Thrombi. — The ultimate fate of thrombi 
depends upon whether they are septic or aseptic. If septic, 
they must undergo disintegration. If aseptic, they may under- 
go organization — a condition that is not a transformation into, 
but is a replacement by, connective tissue. 



46 CIRCULATORY DISORDERS 

They may undergo a central liquefaction or softening. The 
interior is broken down, blood-pigment set free, and leukocytes 
in varying numbers are present. 

Calcification, particularly of small thrombi, giving rise to 
either arterioliths or phleboliths, according to whether they 
occur in arteries or in veins. 

The connective tissue that replaces the thrombi will grad- 
ually undergo contraction until only a hard fibrous mass re- 
mains, the original lesion becoming converted into a scar. 

The new tissue is derived from the endothelium of the blood- 
vessel and the fixed connective- tissue cells. As it forms, the 
thrombus undergoes absorption and breaks down into a mass, 
the granules of which are removed by the leukocytes. 

If the thrombi contain living organisms they will be carried 
through the circulation and give rise to metastatic abscesses 
in various parts of the body. 

The broken-down portions may become lodged in small 
vessels, and, acting as emboli, give rise to the condition known 
as embolism. 

Embolism is the obstruction, complete or incomplete, of a 
blood-vessel due to the lodgment of a foreign body within that 
vessel, the circulating body being known as an embolus. 

The most common variety of embolus is a dislodged portion 
of a thrombus, particularly those that occur upon the valves 
of the heart. Other emboli may be formed by cells of malignant 
tumors, masses of bacteria, blood parasites, particles of fat, 
pigment, air, etc. 

The most common locality for emboli is within branches of 
the pulmonary artery, with immediate death or respiratory em- 
barrassment resulting. The condition is most serious when 
vessels supplying important organs, as the brain, spleen, kid- 
ney, etc., are obstructed. 

The varieties of emboli are: (i) Simple, mechanical, or aseptic; 
(2) specific, infectious, or septic. 

The latter is the more severe, as in it suppurative conditions 
are associated with the mechanical. 

Retrograde embolism occurs when, as in whooping-cough, 
the intrathoracic pressure is increased. An embolus in the 



EMBOLISM 47 

inferior vena cava may be carried in a direction opposite to 
the blood-current and be thus conveyed into the liver through 
the hepatic vein. 

Crossed or paradoxic embolism occurs when the foramen 
ovale remains patulous. In this condition an embolus may 
pass directly from the venous to the general circulation with- 
out going through the pulmonary vessels. 




Fig. 4. — Infectious Embolism of the Kidney Following Endo- 
carditis and Showing Groups of Staphylococci in a Glomerulus 
(Diirck). 



The results of embolism are numerous: 

1. Thrombosis is a consequence of the stoppage of the flow 
of blood by the foreign body. The resulting thrombus may be 
much more extensive than the primary embolus. 

2. Inflammation of the vessel walls is usually the result of 
the lodgment of the embolus, particularly if it is of the infec- 
tious type. 

3. Atrophy may follow if the blood-supply is not quite 



48 CIRCULATORY DISORDERS 

enough for the normal demands, but is yet sufficient to pre- 
vent actual death of the tissues. 

4. Necrosis when the nutrition of a comparatively small 
area is cut off. Occurs chiefly in the internal organs. 

5. Gangrene may result if the main artery of a part has been 
obstructed and the collateral circulation has been insufficient 
or unable to supply the demands. 

6. Aneurysmal dilatation, especially in the brain, sometimes 
results. 

7. Infarction. 

Infarction. — An infarct is the area of degeneration and in- 
flammation produced by embolism in an end-artery or where 
there is an absence of adequate anastomosis. The act of ob- 




Fig. 5. — Part of Spleen the Seat of Multiple Anemic Infarcts 

(Coplin). 

struction constitutes infarction, and must be sufficiently sudden 
to prevent the establishment of any collateral circulation. 

Infarcts occur chiefly in the so-called end-arteries of Cohn- 
heim — those that terminate in veins or capillaries without 
anastomosis with an artery. They are found particularly 
in the kidney, spleen, base of the brain and lungs, and some- 
times in the heart. 

The varieties of infarcts are: (1) Anemic or white; (2) hemor- 
rhagic or red. 

The anemic occur more commonly in solid organs, such 
as the kidney; the hemorrhagic, in organs whose structure is 
loose, as the lungs. The spleen may be the seat of either form. 

An anemic infarct is one in which there is an absence of 
blood. The essential cause of this form is probably the rela- 



INFARCTION 49 

tively rapid death of the tissues with coagulation before the 
capillary anastomoses have widened sufficiently to cause hemor- 
rhage. There is usually a narrow hemorrhagic zone surround- 
ing the lesion. 

In this type there is probably present a secondary blood- 
supply sufficient to prevent the occurrence of coagulation 
necrosis. 

A hemorrhagic one is where the obstructed area is full of 
blood. It may be the result of a back flow of blood from 
the veins (Cohnheim's theory) or from free capillary anas- 
tomosis. The latter would be particularly apt to occur when 
the local or general blood-pressure was previously elevated; 
or when the lodgment of an embolus caused a reflex contrac- 
tion of the surrounding vessels and thus brought about an 
overflow of blood into the occluded area through the capillary 
anastomoses. Another theory is that the blood does not escape 
until there has been some degeneration of the vessel walls. 

When the blood is cut off a conical shaped area of tissue is 
deprived of nutrition. As a result, necrosis soon starts in. 
The apex of this area is directed toward the interior of the 
organ, the base to the external surface. The base will be swollen 
and project above the surface of the surrounding tissues. 

The infarct is, as a rule, firmer than the rest of the organ, 
except when it occurs in the central nervous system, where it 
is usually softer; the firmness depending upon the amount of 
coagulable material present. 

. Infarctions of the lung are unusual, as in that organ the 
capillaries are comparatively large, and the anastomosis be- 
tween the pulmonary and bronchial arteries may be sufficient 
to prevent necrosis. To have infarcts occur within the lung, 
that organ must have been the seat of previous disease. 

Results. — Infarction is always accompanied by necrosis and 
fatty degeneration, (i) The tissue may be restored by ab- 
sorption and by collateral circulation. (2) It may be replaced 
by connective tissue with the formation of a scar. (3) It may 
become encapsulated. (4) Very rarely an infarct may undergo 
liquefaction necrosis with cyst formation, particularly in the 
brain. 



50 CIRCULATORY DISORDERS 

Edema, or dropsy, is an excess of a clear watery fluid within 
the tissues between the cells. This fluid differs from the 
blood-plasma in that it has less albumin, is of a lower specific 
gravity, is rich in salts, but does not coagulate spontaneously, 
as it contains very little fibrin. This is called a transudate to 
distinguish it from the fluid present in inflammations, the latter 
being called an exudate. 

It may be caused by: 

i. Differences of pressure, a filtration process. 

2. An increased secretion by the endothelial cells of the 
vessels. 

3. Osmosis, resulting from variations in the relative concen- 
tration of salts, particularly sodium chlorid, on either side of the 
osmotic membranes, the cell walls. 

4. The most satisfactory explanation of the occurrence of 
edema can probably be based upon the properties of colloidal 
(non-crystalloid) bodies such as gelatin and, presumably, other 
proteins. If dried gelatin is placed in water it will absorb a 
definite quantity of that water and will swell up to a certain 
point. If the water be slightly acidified the amount absorbed 
becomes very much greater. It has been shown that an inade- 
quate supply of oxygen results in the production in the tissues 
of acids, particularly lactic acid and carbon dioxid, which, in 
turn, increase the tendency of colloids to take up water; con- 
sequently, edema is brought about. There is probably little of 
it due to increased capillary pressure or to secretory activity on 
the part of the endothelium of the blood-vessels. 

5. Neuropathic edema, as herpes zoster and angioneurotic 
edema, may be due to something more than simple uncompli- 
cated vasomotor disturbances. 

6. Hydrops, or edema ex vacuo, is that which occurs when an 
organ, as a result of atrophy, does not completely fill its cavity, 
the remaining space becoming filled with fluid. It usually 
occurs in the cranial cavity and in the spinal canal. 

The types of edema are as follows : 

1. Congestive edema, the commonest form. Present in cases 
of obstruction to the venous outflow. Possibly the interference 



INTERSTITIAL EMPHYSEMA 5 1 

with the nutrition of the tissues and the changes thus resulting 
play a part. 

2. Edema from lymphatic obstruction does not occur in 
healthy tissues, but does take place if there is some disturbance 
of nutrition in the areas involved in the lymphatic obstruction. 

3. Inflammatory Edema. — Probably due to degenerative 
changes occurring in the endothelial cells of the capillaries and of 
the tissue cells as well. 

4. Toxic Edema. — Various toxic substances circulating in the 
blood have possibly different effects on the capillary walls. 

According to the seat of the edema, special terms are em- 
ployed. 

When the subcutaneous tissues are generally involved, it 
is known as anasarca. Ascites refers to a collection of fluid 
within the abdominal cavity. 

Hydrothorax, a collection within the pleural cavities. 

Hydropericardium, when within the pericardium. 

Hydrocephalus, fluid within the ventricles of the brain. 

Hydrocele, when within the tunica vaginalis testis. 

The common clinical causes are: (1) Cardiac insufficiency, 
the edema usually first noticed about the ankles. (2) Kid- 
ney disease, first seen about the eyes. (3) Cirrhosis of the 
liver, accompanied by ascites. (4) Anemia and cachexia. 
(5) Pressure upon the veins or lymphatics. 

Under the microscope the cells of the involved tissues will 
appear more or less widely separated and in some instances 
may be vacuolated. 

Interstitial emphysema is an infiltration of the tissues by 
gas, usually the result of some injury involving the respiratory 
tract. It may be due to the presence of some gas-producing 
bacteria, such as the bacillus of malignant edema or the Bacillus 
aerogenes capsulatus, within various organs, particularly the 
uterus and liver. It is a comparatively rare condition. 



CHAPTER IV 

RETROGRESSIVE PROCESSES 

Aplasia signifies a total failure of development of a part. 
Hypoplasia is an incomplete development. 

ATROPHY 

Atrophy refers to a decrease in the size and in the func- 
tional activity of a part. It may be general or local. 

In general atrophy the entire body wastes, a condition known 
as emaciation. It may be the result of lack of food, of starva- 
tion, or of disturbances of trophic influences with disorders of 
metabolism. 

In local atrophy certain portions undergo changes which may 
be either simple, degenerative, or numerical, as the latter is some- 
times called. 

In the simple variety the individual cells undergo a de- 
crease in size. 

In the degenerative the number of cells is reduced as a result 
of disease. This is not considered a condition of true atrophy. 

Atrophy may be brought about by there being no longer 
a demand made upon the part. Through lack of use the cells 
become smaller. 

Old age is often accompanied by atrophy; is seen particu- 
larly in the sexual organs and in the loss of the elastic tissue of 
the skin. 

Pressure is one of the commonest causes; occurs as a result 
of tight lacing, etc. 

Interference with the blood-supply on account of the part 
not being supplied with a proper amount of nutrition. 

Disturbances of the trophic functions, as in poliomyelitis. 
52 



PARENCHYMATOUS DEGENERATION 53 

The atrophied part will be smaller than normal, and fre- 
quently very irregular, causing elevations and depressions. 
Microscopically, the cells will be reduced in size, more or less 
degenerated, and frequently pigmented. The latter condition 
occurs commonly in the heart and is known as brown atrophy. 

DEGENERATIONS 

Degenerations of cells can be divided into two forms: 

i. Infiltrations, in which abnormal substances are deposited 
within the cells. 

2. Metamorphoses, in which the protoplasm of the cell is 
transformed into abnormal substances. 

"It was thought, but now seems less certain, that we could 
distinguish two processes which might accompany each other: 
one, the change wrought in the cytoplasm itself, leading to the 
appearance in the cell of such changed products; the other 
characterized by the appearance in the cytoplasm of substances 
obtained from outside the cell, and, it may be, imperfectly 
handled by the cell. It was thought that the former were 
degenerations proper and the latter infiltrations, but further 
study shows that it is becoming increasingly difficult to separate 
the two; that, in fact, they are too closely related to permit of 
being considered apart. Especially does it seem to be that true 
infiltration by itself is a rare occurrence. 'Infiltrated' materials, 
as fat, glycogen, etc., probably are the result of synthetic 
processes." 

The changes in the cell may also be either quantitative, as 
when a normal substance is present in an abnormal amount; 
or qualitative, when there is an abnormal substance present. 

Necrobiosis refers to the molecular or cellular death of a part. 

Parenchymatous Degeneration or Cloudy Swelling. — In 
it the protoplasm of the cells contains an increased amount of 
protein substances. It accompanies very slight disturbances 
of nutrition, such as occur in inflammation; is found in all 
infectious diseases and intoxications, possibly as a result of 
increased bodily temperature, most likely as a result of dis- 
turbances of metabolism. 

Although all the cells of the body, both glandular and stroma, 



54 RETROGRESSIVE PROCESSES 

may undergo this change, they are not equally affected, the 
glandular ones being more liable to injury. The secreting cells 
have as their function the removal of certain substances from 
the body. If the blood contains injurious materials, these cells 
naturally will be the first affected, as they are the more inti- 
mately concerned. 

This degeneration may follow extensive superficial burns, 
probably as a result of the action of the poisonous substances 
absorbed. 

Microscopically the individual cells will be swollen and larger, 
more granular, and more opaque than normal on account of the 
presence of minute granules; the nucleus, consequently, may be 
obscured. These latter are insoluble in alcohol and ether, but 
are dissolved by alkalies and weak acetic acid. 

The function of the cell is more or less disturbed, but com- 
plete recovery frequently occurs. If, however, the cause 
persists, fatty metamorphosis results. 

Fatty infiltration is the deposit of fat within the cell or inter- 
cellular tissues. In all parts of the body, except the liver, the 
connective tissue is affected. In this organ the secreting or 
parenchymatous cells are involved. May be general or local. 
It may occur in cells that normally contain no fat, or else appear 
in excess in cells that do contain it. 

The fat contained within the cells is made up of neutral 
palmitin, olein, and stearin. 

Fatty infiltration may be hereditary, as obesity in succes- 
sive generations; may result from excessive nutrition, particu- 
larly if combined with lack of exercise. 

The use of alcohol, especially in the form of malt liquors. 
The alcohol, being easily oxidized, probably takes the place of 
the fats which remain unused. 

Anemia, on account of the insufficient oxygenation of the 
tissues. 

In certain cachectic conditions, as in phthisis; where the liver 
is frequently filled with fat. 

The most common seats are the subcutaneous and subserous 
tissues, the omentum and the mesentery, in the liver, heart, kid- 
ney, and between the muscle-fibers. 



FATTY INFILTRATION 



55 



Certain other regions, such as the subcutaneous tissue of 
the penis, nose, ear, lips, and eyelids, are never involved. 

An organ the seat of fatty infiltration is larger, paler, mottled, 
streaked or diffusely yellow, softer, more friable, and greasy on 
section. 




Fig. 6. — Fatty Infiltration of the Liver (McFarland). 
a, Periportal connective tissue; b, fat drops in liver cells. 



Under the microscope the fat may be found either inside 
or outside of the cells. If outside, it is most marked along the 
fibrous bands. 

Inside the cell, particularly the glandular variety, the fat 
occurs in droplets which tend to enlarge and coalesce. The 
nucleus is displaced, giving the "signet-ring" appearance, cr 
obscured; is seldom destroyed. The cell wall remains intact. 

The tests for fat are sudan III, which stains it scarlet, or 



56 RETROGRESSIVE PROCESSES 

a i per cent, solution of osmic acid, which stains black. It 
is soluble in alcohol, ether, and xylol; insoluble in water, acids, 
and alkalies. 

Adipocere refers to the transformation of the fats into a wax- 
like substance most common in bodies that have been buried 
in damp earth. 

Fatty metamorphosis is a conversion of the cell protoplasm 
into fat. 

Generally speaking, the causes of cloudy swelling will bring 
about fatty degeneration if they are severe enough or act for 
a sufficiently long time. It occurs in senility, particularly when 
associated with marked arteriosclerosis and atheroma; in 
anemia, either as a result of hemorrhage or in diseases such as 
leukemia and pernicious anemia. The condition is probably 
more widespread in the latter than in any other disease. Occurs 
also in long-continued and high fever. 

The most important substances causing the metamorphosis 
are the poisons, as the metallic salts, chloroform, coal-tar 
products, etc., and those formed by micro-organismal activity, 
as in yellow fever. 

The fat present in the cells is either (1) formed by actual 
disintegration of the protoplasm of the cells, or (2) is taken 
up by the cells from the blood and remains unaltered, owing to 
defects in the vital power of the cell to assimilate it. 

This condition may result from — 

1. Insufficiency of the supply of nutriment. 

(a) The blood-supply may be actually diminished. 

(b) There may be increased work without a corresponding 
increase in the blood-supply. 

(c) Actual deficiencies in the blood may impair its nutritive 
value, as diminution in the hemoglobin or of the corpuscles. 

2. The failure of the cell to make use of the material placed 
at its disposal is probably the more important cause. 

(a) The result of bacterial toxins. 

(b) The influence of inorganic poisons. 

(c) A senile change dependent upon the exhaustion of the 
inherited vital capacities of the cells. 

Organs undergoing this change are generally smaller and 



HYALINE METAMORPHOSIS 57 

paler, yellowish, soft and flabby, and easily friable; they may 
undergo caseation. 

The liver in yellow fever is a typical example. 

Microscopically the cell protoplasm contains a large number 
of minute droplets that rarely coalesce. The nucleus is soon in- 
volved and ultimately is destroyed. The entire cell may break 
down into a fatty granular mass, sometimes called a "compound 
granule cell." Granules may be so small that their character 
cannot be recognized except by special staining. 








Fig. 7. — Hyaline Degeneration of an Ovarian Capillary. Oc. 2; 
ob. 9 (McFarland) . 



To distinguish between fatty metamorphosis and fatty infil- 
tration is frequently not only difficult, but impossible, especially 
so in the liver. The droplets may coalesce in metamorphosis 
and remain separate in infiltration. 

Crystals of margarin and the notched rhombic plates of 
cholesterin are frequently found in the fatty areas. 

Hyaline metamorphosis is a conversion of cells and inter- 
cellular substance into hyaline material. 



58 RETROGRESSIVE PROCESSES 

The cells of the connective tissue are most frequently in- 
volved, but epithelial and muscle cells may be affected. 

The hyaline material occurs in the form of granules, is 
glistening and waxy, and with Van Gieson's method stains in- 
tensely red. Has no specific action with iodin. 

It is at times scarcely distinguishable from amyloid meta- 
morphosis. 











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Fig. 8. — Hyaline Degeneration of the Reticulum of a Lymph-cland 
in Tuberculosis. X 280 (Diirck). 
Among the lymphocytes are seen single reticular fibers, which are 
greatly thickened and transformed into shining, homogeneous, non-nucleated 
bars (1). 

It is found as a result of infectious diseases, septic processes, 
in chronic intoxications, such as lead-poisoning, and in new 
growths. Its formation is probably dependent upon some mal- 
nutrition of the tissues. Generally this form of degeneration is 
not sufficiently extensive to be recognized by the naked eye. 

The most common site is in the endothelial and subendo- 
thelial tissues of the blood-vessels. The lumen will be narrowed 
or obliterated according to the extent of the thickening of the 
wall. 



COLLOID METAMORPHOSIS 59 

It also frequently occurs in the interstitial tissues, as be- 
tween the renal tubules, between muscle-fibers, hepatic cells, 
and in the reticulum of lymph-nodes (Recklinghausen's de- 
generation). A third site is within the cells, particularly those 
of mesodermic origin. 

It is either formed within the cell or, being formed else- 
where, has been brought to and deposited within the cell. 

Mucoid or myxomatous metamorphosis is the conversion 
of cells and intercellular substances into mucin. 

Mucin is insoluble in water, but will absorb it; is soluble 
in alkaline solutions, but is precipitated by weak acetic acid. 
When boiled with acids, will reduce Fehling's solution. 

Either epithelial cells or the intercellular substances may 
undergo mucoid change. The latter is the more truly a meta- 
morphosis. 

It occurs in epithelial cells in all forms of catarrhal inflam- 
mation, in the cells of epithelial cysts, and in some carcinomata. 

It is found in the interstitial tissues in both epithelial and 
connective-tissue growths, in some inflammatory conditions, 
and in myxedema. 

The mucous membranes will be covered by a coat of thick, 
stringy, and viscid exudate. The underlying tissues may or may 
not show congestion. 

Connective tissues will be more or less soft, slightly swollen, 
and will tear easily. If the condition is very much localized, 
cysts rilled with mucin may be found. Three substances 
closely related are included under the heading of Myxomatous 
Metamorphosis: mucin, pseudomucin, and paramucin, each one 
differing slightly from the others in its reaction. 

The typical mucoid cell is the so-called "goblet-cell" that is 
found in the large intestine. 

The mucoid change looks under the microscope very much 
like edema. The cells are widely separated and the structure 
of the tissue is poorly defined. The cells frequently stain 
poorly and degenerate. 

Colloid metamorphosis is the transformation of the cell sub- 
stance into a thick, sticky substance known as colloid. It is 
found only in epithelial cells. It is not precipitated by acetic 



60 RETROGRESSIVE PROCESSES 

acid or by alcohol, nor does it swell in water. It usually stains 
orange color with Van Gieson. 

It is normally found in the acini of the thyroid gland and 
in the pituitary body. It is frequently found in parovarian 
cysts, in goiter, in the tubules of the kidney in chronic nephritis, 
and in the prostate gland. 

In cysts the colloid material is generally contained in many 
small cavities, giving rise to a honeycomb appearance. It may 



%< - 


* r* - ' ■ 


4 










ill 



Fig. 9. — Colloid Degeneration of the Thyroid Gland, Showing 
Masses of Colloid Matter in the Gland Acini (Karg and Schmorl). 

be transparent, yellowish, bluish, or chocolate color, according to 
other substances present. 

Amyloid metamorphosis is a degeneration of the connective 
tissues into an abnormal substance giving an amyloid reaction. 
The origin of this material is obscure. It may be formed in 
loco, but more probably is brought to the tissue from some other 
part of the body. It does not exist as such in the blood, but is 
very probably derived from substances contained in that fluid. 
Some believe that the leukocytes, others that the erythrocytes, 
are the cells from which it is derived. 



AMYLOID METAMORPHOSIS 



61 



It is frequently called waxy, lardaceous, or "bacony" disease; 
is found in the intercellular portions of the connective tissues 
and not in secreting cells. 

It is found as a result of long-continued suppuration and 
ulceration, such as occur in diseases of the bone, chronic tuber- 
culosis, syphilis, leukemia, and dysentery. 

The organs most commonly affected are the spleen, liver 
and kidney, the larger blood-vessels, the mucous membrane 
of the intestines, the lymph-nodes, and the heart. 



T' 






Fig. io. — Amyloid Degeneration of the Liver. X 98 (Diirck). 
1, Central vein. Portal capillaries surrounded by homogeneous 
masses and bands; the epithelial lining distinct. Columns of liver cells 
compressed to narrow, atrophic strips. 

The involved organs are generally pale, larger, firmer, and 
heavier than normal, and with rounded edges. The cut sur- 
face is smooth, glistening, and transparent, either diffuse or 
localized. The usual sites of the degeneration are the walls of 
the capillaries, in the intima and media, the adventitia being 
rarely affected. 

In the kidney the capillaries of the glomeruli are first at- 



62 RETROGRESSIVE PROCESSES 

tacked, converting the bodies into waxy, homogeneous masses; 
finally the connective tissue may be involved. 

In the liver the amyloid substance is found between the peri- 
portal connective tissue and the central vein, in the interme- 
diate zone which is supplied by arterioles and capillaries of the 
hepatic artery. In the spleen it may give rise to the "sago 
spleen," a condition which is brought about by the formation 
of amyloid material in the Malpighian bodies. Later on, the 
organ may become very extensively involved. In some cases 
the vessels in the trabecular of the organ may be the seat of the 
metamorphosis. 

When amyloid material has been once deposited it is practi- 
cally never removed. It is insoluble in water, alcohol, ether, 
dilute acids, alkalis, etc. Resists peptic digestion and with- 
stands decomposition for a long time. Unless special staining 
methods are employed, it frequently cannot be distinguished 
from hyaline degeneration. 

When the affected tissue is placed in Lugol's solution (iodin i, 
potassium iodid 2, water 100) the amyloid substance becomes 
a mahogany brown. If stained in 5 per cent, aqueous gentian- 
violet the amyloid will appear pink; the normal tissues, blue. 

If after staining in iodin, weak sulphuric acid (5 to 10 per 
cent.) is added, the amyloid will turn blue. 

Corpora amylacea, or amyloid bodies, are found in the pros- 
tate gland, in lymphatic nodes, and in the central nervous sys- 
tem. They are concentrically striated like a starch granule, 
and although in their reaction they may resemble starch and 
amyloid, they are probably neither. 

Glycogenic infiltration is a deposit of glycogen within the 
cells. It is found normally in small amount throughout the 
body except in the mammary glands and central nervous system. 

It is greatest in amount in the cells of the liver, in voluntary 
muscles, and in the kidneys; is also present normally in the blood, 
both in the plasma and in the cells, particularly the polymorpho- 
nuclear leukocytes. It is also commonly found in malignant 
tumors of mesodermic origin (sarcomata). 

The origin of the glycogen is not clear; it is a carbohydrate, 
but seems to be derived from protein and carbohydrate sub- 



PIGMENTARY INFILTRATION 63 

stances. Glycogen is most frequently found in the condition 
known as diabetes. 

Tissues containing large amounts of glycogen may have 
a distinct hyaline appearance. The reactions, however, differ, 
as it is soluble in water, but not in alcohol, ether, or xylol; is 
colored a brownish red on the addition of tincture of iodin 1 
part, absolute alcohol 4 parts. The brown is not changed to 
blue on the addition of sulphuric acid. 

Microscopically, glycogen occurs in the cells in clear, colorless 
droplets, usually near the nuclei. 

Serous or edematous infiltration is a condition of dropsy 
of the cells. All kinds of cells may be involved, but it is most 
common in the epithelial. It is an absorption of an excess 
of plasma by the cells. 

It may accompany general dropsy or result from inflam- 
mation; is also found in tumors. 

The part involved is usually enlarged, spongy, and edem- 
atous. ■ 

The cells are distended and filled with large and small vacuoles 
in the protoplasm and at times within the nucleus. 

Pigmentary infiltration is the deposit of pigment within 
the tissues. 

According to their origin, pigments may be divided into 
four classes: 

1. Those derived from outside of the body. 

2. Those formed from hemoglobin and its derivatives, the 
hematogenous pigments. 

3. The hepatogenous or biliary pigments. 

4. Metabolic pigment; that resulting from cellular activity 
within the body is known as melanin. 

The hematogenous pigments are three — hemoglobin, hemo- 
siderin, and hematoidin. 

Hemoglobin is dark red in color, amorphous, contains iron, 
and is soluble in alcohol, ether, and chloroform. It is recog- 
nized chemically by the addition to the suspected fluid of a few 
drops of a fresh tincture of guaiac and then followed by an 
ethereal solution of hydrogen dioxid. The mixture, which is at 
first milky white, turns a deep blue. 



64 RETROGRESSIVE PROCESSES 

If the dried blood is dissolved in normal salt solution, then 
warmed and evaporated, glacial acetic acid added and warmed, 
small reddish-brown rhombic plates of hemin appear. 

When brought in contact with sulphuretted hydrogen, 
hemoglobin combines and forms ferrous sulphid, which is 
black. This gives rise to the bluish discoloration of the ab- 
dominal wall that appears when decomposition has occurred. 

Hemoglobin is set free from the erythrocytes through hemo- 
lysis, either within the vessels or when the blood has escaped 
into the tissues. The surrounding structures will be diffusely 
stained. This is commonly seen postmortem, particularly in 
those parts of the liver that are in contact with the intestines. 
When it is set free within the vessels during life, it may be de- 
posited within the lymph-nodes, spleen, and kidney, forming 
pigment metastases. 

Hemosiderin is yellowish or brownish in color, amorphous, 
contains iron, and is insoluble in water, alkalis, alcohol, ether, 
xylol, and chloroform. 

On the addition of potassium ferrocyanid and weak hydro- 
chloric acid it turns blue (Prussian blue reaction) . 

It occurs in the blood, in cells and intercellular tissues, as a 
consequence of recent hemorrhages; apparently results from 
the slow destruction of the erythrocytes. 

The granules are taken up by the phagocytes and may be 
finally removed by them. Cells filled with the granules are 
frequently found in the sputum in cases of chronic congestion of 
the lungs. 

Hematoidin, similar to bilirubin, is a reddish-brown pigment, 
found in the form of rhombic crystals; does not contain iron, 
is insoluble in water, alcohol, or ether, but is soluble in chloro- 
form. It is found at the seat of old hemorrhages, and is gener- 
ally considered a later form of hemosiderin. 

The causes of hematogenous pigmentation can be divided into 
local and general. 

Local. — Hyperemia, venous stasis, inflammation, hemorrhage. 

General. — Hemolysis resulting from animal poisons, bac- 
terial toxins, chemicals. Action of parasites, as in the destruc- 
tion of the red cells in malaria. 



PIGMENTARY INFILTRATION 65 

Hepatogenous pigmentation is due to the presence of pig- 
ments derived from the bile, bilirubin, which is similar to 
hematoidin, and its oxidation product, biliverdin. The bili- 
rubin is formed by the hepatic cells from hemoglobin, from 
destroyed red blood-cells, the iron being retained in the liver 
and not cast off along with the pigment. It is soluble and conse- 
quently is taken up by the blood and carried throughout the 
body, giving rise to the discoloration known as icterus or jaun- 
dice. Both cells and intercellular substances may be diffusely 
stained, or, if the condition is of long standing, greenish-yellow 
crystals or granules may be found. 

The fluids of the body will also be discolored. 

The presence of these pigments can be recognized by Gmelin's 
test with fuming nitric acid, which will give a play of colors at 
the point of contact. 

This condition may be caused by (1) obstruction to the 
outflow of bile through the ducts, obstructive jaundice; (2) pos- 
sibly through excessive bile formation resulting from hemo- 
lysis, hematogenous jaundice; (3) hepatic disorders, as acute yel- 
low atrophy of the liver. 

Metabolic pigmentation or melanosis is a discoloration of the 
tissues through the formation of melanin by the cells. 

The tissues are colored yellow, brown, or black. 

Under the microscope melanin occurs as dark granules in the 
cells and intercellular tissues. Is normal in the pigmented cells 
of the retina, choroid, hair, and skin. 

Its chemistry is not well known. It contains sulphur, but little 
or no iron, is insoluble in water, alcohol, and ether, but soluble 
in boiling alcohol, acids, and alkalis. 

It is found commonly in the melanotic sarcoma. It generally 
tends to destroy the cells in which it is contained, and for 
some reason such tumors are generally more rapidly metastatic 
and fatal than the non-pigmented forms. 

In Addison's disease there is a general bronzing or melan- 
osis of the skin. In many cases this condition seems to follow 
extensive disease of the adrenals. 

In malaria the pigment present is probably not melanin, but 



66 RETROGRESSIVE PROCESSES 

is similar to hematin, and is formed by the action of the 
malarial parasite upon hemoglobin. 

Certain muscular degenerations, as in "brown atrophy" 
of the heart. Is questionable whether such granules are true 
melanin. Various skin affections, as freckles, or lentigo, chloasma, 
and also in pigmented moles. 

Extraneous pigmentation results from the introduction of 
coloring-matters into the body from the outside. The tissues 







>K1 



V 

Fig. ii. — Anthracosis of the Lung. X ioo (Diirck). 
The lung tissue is very much indurated as the result of newly formed 
connective tissue in which are embedded star-shaped masses of fine, granu- 
lar, blackish pigment of inhaled coal particles. 

most commonly affected are those of the lungs, giving rise to the 
condition known as pneumonokoniosis . 

Anthracosis, or the deposition of coal-dust, is the most fre- 
quent, the lung being colored more or less black according to the 
amount present. 

Siderosis results from the inhalation of fine particles of iron. 

Chalicosis, caused by the presence of lime in the lungs. 

Argyria is a bluish-gray discoloration of the skin resulting 
from the long-continued use, internally, of nitrate of silver. 



CALCAREOUS INFILTRATION 



67 



Tattoo marks following the introduction of insoluble coloring 
substances into the skin. 

Calcareous infiltration or calcification refers to the deposit of 
earthy salts within the tissues. It occurs in consequence of a 
deficiency of oxygen and an excess of carbon dioxid in the tissue 




Fig. 12. — Calcareous Infiltration of the Wall of a Small Artery 
From the Wall of a Gumma of the Liver. Zeiss, Oc. 2; ob. D. D. 
(McFarland). 

In addition to the calcification that has occurred in the media contig- 
uous to the fenestrated elastic layer, there is marked syphilitic endarteritis 
with great reduction in the caliber of the vessel from proliferation of the sub- 
endothelial tissue of the intima. 



juices, which causes a deposit of the carbonates and phosphates 
of magnesium and calcium. Oxalates are also generally present. 
This process is found only in those tissues that are either 
completely destroyed or else undergoing degeneration as a 
result of imperfect nutrition. 



68 RETROGRESSIVE PROCESSES 

The deposition of the salts is probably due to a lack of oxygen 
and an increase of carbon dioxid in the tissues, on account of 
which there is a precipitation of the magnesium and calcium 
carbonates and phosphates. 

It is commonly seen in the fibrous framework, but may 
be found within the cells as well. The favorite site is in the 
connective tissues that have a poor blood-supply, such as 
cartilages, the walls of blood-vessels, also in old inflamma- 
tory areas, in regions of degeneration, such as infarcts, around 
foreign bodies, and in tumors, particularly in degenerated uterine 
fibroids. Is sometimes seen in the ganglionic nerve-cells, in the 
"pearls" of epitheliomata, and in the tumors of the nervous 
system called psammoma, which are made up of masses of 
salts deposited in the tissues. The most common seat is 
probably in the arterial system. It is often the sequel of a 
senile atrophy of the elastic tissue of the vessel wall, along 
with degeneration of the connective tissue and a general 
fibrosis. 

The valves of the heart frequently undergo calcification, as 
well as the walls of the aorta, the coronary, and cerebral arteries. 

Microscopically the salts may appear as granules, spicules, 
plates, or crystals. 

If within the cellular protoplasm the granules may be so 
numerous as to hide the nucleus. 

The salts are insoluble in ether, but give off carbonic acid 
gas when dissolved by hydrochloric acid. They also stain 
very deeply with hematoxylin. 

Uratic infiltration in the form of sodium biurate occurs 
in the cartilages and fibrous tissues in gout. Ordinarily the 
above salt is soluble in the blood, but under certain constitu- 
tional conditions it is deposited as an insoluble salt. These 
collections are called tophi, and are found particularly in the 
joints. An admixture of calcium and magnesium carbonate 
and phosphate is usually present. 

Necrosis is the death of a part of a living organism. It is 
the death of a part as distinguished from the death of the 
entire body (somatic death). The causes of necrosis are (i) 
local injury, (2) vascular obstruction, and (3) trophic disturbances. 



NECROSIS 69 

Under the local injuries are included those that are me- 
chanical, chemical, thermal, and bacterial. 

Mechanical injuries may cause destruction of the cells directly 
or by interference with the blood-supply. Pressure of foreign 
bodies will often bring about necrosis. 

Chemical substances such as the acids and alkalis may 
cause destruction of the tissues. 

Thermal injuries, those from extreme heat or cold, will more 
or less quickly destroy the vitality of the cells. 

Bacterial products acting as toxic agents will frequently 
cause necrosis and gangrene. 

If vascular obstruction take place suddenly, the nutri- 
tion will be shut off and necrosis result. 

Trophic disturbances will lessen the resisting power of the 
tissues with subsequent necrosis. This is seen in decubitus or 
bed-sore that occurs in various forms of spinal disease. The 
perforating ulcer of the foot is another example. 

The cells hi the necrosed areas will show different stages 
of disintegration. The cell wall may remain, but the cyto- 
plasm will not stain. There may be complete destruction 
and breaking down of the cell. The granules in the pro- 
toplasm disappear, and it in turn becomes cloudy, gradually 
breaks up, and vacuoles form. The nucleus may lose its 
staining power or may undergo destruction in one of two 
ways: By karyorrhexis , a breaking down of the chromatin 
into granules, or by karyolysis, a liquefaction of the nuclear 
constituents. 

Necrosis may be of different varieties. 

Coagulation necrosis is a form of death of those tissues freely 
supplied with lymph, accompanied by a consolidation of the 
protein contents. It is a change similar to the coagulation of 
the blood. The fibrin ferment present acts upon the fibrin 
factors and fibrin is formed. 

It is found in thrombi, blood-clots, and interstitial hemor- 
rhages. 

Occurs in various inflammatory exudates, particularly in 
croupous pneumonia and diphtheria, and in infarcts. 

The seat of the necrosis is firmer and paler than normal, 



70 RETROGRESSIVE PROCESSES 

and dry. Later on it may become softer and discolored as a 
result of disintegration of blood. 

Caseous necrosis is a condition in which the tissues have 
been transformed into a cheese-like substance. 

It is found only as a sequel to pre-existing coagulation necro- 
sis. Is found most commonly in tuberculosis, but occurs in 
tumors and in syphilis. 

Surrounding the area of caseation there is generally a zone 
of coagulation. 

Liquefaction or colliquation necrosis is the death of the tis- 
sues with liquefaction. It occurs in those tissues that contain 
little protein substance, especially in anemic infarcts of the 
brain. The nervous tissue undergoes a softening, becomes semi- 
fluid, and eventually liquid, remaining as a colliquation cyst. 

Focal necrosis is a condition in which minute areas of necrosis 
scarcely visible to the naked eye occur, particularly in the 
lymph-follicles and the liver in various forms of severe infection. 
They may be due to minute thrombi or to alterations in the 
endothelium of the capillaries. 

Gangrene may be of two forms — dry and moist. The tissues 
involved are those that are exposed either directly or indirectly 
to the atmosphere. 

Dry gangrene, or mummification, is the death of tissues with 
subsequent drying. It occurs particularly in the extremities 
of old people or of those who are much debilitated. Is gener- 
ally due to some obstruction of slow formation of the arterial 
system, by a thrombus, an embolus, by disease of the walls, by 
a spasmodic contraction of the vessel, or by pressure from the 
outside. It is usually circumscribed, there is very little odor, 
the tissues become almost black and mummify through evapora- 
tion of the moisture. 

Moist gangrene is the death of living tissues plus an infection 
by bacteria that are capable of producing putrefaction. 

It occurs in those parts that are exposed to the air, either 
directly or indirectly. 

It takes place in people who have previously been in good 
physical condition, usually being the result of extensive venous 
obstruction combined with a weak arterial supply. 



GANGRENE 



71 



The part involved undergoes necrosis and afterward be- 
comes infected. It becomes greenish black, gas blebs appear 




Fig. 13. — Senile Dry Gangrene op the Lower Extremity, Showing 
Line of Demarcation (Hektoen). 



on the skin or in the tissues, and an extremely offensive odor 
develops. 

The cells break down completely, hemorrhage takes place 
as a result of destruction of the blood-vessels, and many toxic 



72 RETROGRESSIVE PROCESSES 

substances are formed. They resemble the alkaloids and may 
bring about marked disturbances of the organism. This form 
of gangrene may terminate in several ways. 

The dead tissue, sphacelus or slough, gives rise to a zone of 
inflammation, which is known as the line of demarcation, at 
the point of contact with the healthy tissue. This zone, as a 
rule, indicates the limits of the gangrenous process. At this 
site there is a constantly increasing interval between the dead 
and living tissue. The tissues here break down and form the 
line of ulceration. It is an attempt of nature to throw off the 
foreign substance and at the same time to form new tissue. 
The process is known as exfoliation. If the necrotic tissue 
cannot be thrown off, as is the case when bone is involved, 
there will probably be a sequestrum formed. This is the result 
of new bone forming around the dead tissue before there has 
been time for it to exfoliate. 

If the degenerated area cannot be discharged, as when the 
internal organs are involved, it frequently becomes surrounded 
by a capsule of connective tissue that protects the neighboring 
parts — process of encapsulation. Again, the necrotic tissue 
may disappear through absorption, may calcify, or undergo 
cicatrization or organization. 

Fat necrosis is a peculiar type occurring usually in the fat 
within the abdominal cavity. In nearly all cases it seems to be 
dependent upon some disease of the pancreas, particularly 
hemorrhagic pancreatitis. 

It is the result of the splitting of the fat molecule into its 
fatty acid and into glycerin. The fatty acids are deposited as 
crystals and unite with calcium to form salts. 

These areas are generally about the size of a pea, whitish 
in color, soft or gritty. A zone of inflammation may or may 
not surround them. 

Death is the cessation of life — meaning that all the com- 
ponent parts of the organism cease to live. 

Up to a certain time the cells of the body are able to supply 
all the needs, but eventually the natural term of life is reached 
and the cells gradually fail to support the tissues. Such a 
condition would be termed physiologic death. If, however, 



DEATH 73 

it follows as a result of diseased processes, it would be 
pathologic. 

The two, however, cannot be strictly separated, as in old 
age there are always conditions present that are not normal. 

The conditions absolutely necessary for life are a continua- 
tion of circulation, respiration, and innervation. 

There may be a destruction of certain portions of the body 
without death following, but a cessation of any of the above- 
mentioned functions brings about dissolution. This is known 
as somatic death, and, according to which function ceased, it is 
said to have taken place by syncope, asphyxia, or coma. 

Molecular death refers to the death of cells. 

Signs of death are those that indicate that the organism has 
ceased to live. Cessation of the necessary functions may give 
rise to apparent death, but without other indications it cannot 
be diagnosed with certainty. 

The necessary signs are: 

Algor mortis, a fall of the temperature to that of the sur- 
rounding atmosphere. Following tetanus it may, however, be 
preceded by a distinct rise, continuing for some hours. 

Livores mortis, or postmortem lividity, are the discolored areas 
that appear in the dependent portions of the body as a result 
of the dilatation of the blood-vessels. It is often of great im- 
portance to distinguish this condition from the discoloration fol- 
lowing a blow. In the first the color will disappear on pressure, 
but in a bruise it will remain, as the blood is not within the 
vessels. 

Rigor mortis, or postmortem rigidity, is a stiffness due to the 
coagulation of the albumin of the muscles with the formation of 
myosin. It is first seen in the muscles of the neck and jaws, 
then extends downward, involving the entire body. 

It generally comes on within four to twelve hours, but may 
appear immediately or be delayed for twenty-four hours. 
At the end of twenty-four to forty-eight hours it usually passes 
off. 

If death has occurred suddenly and the individual is in 
good health, it appears much more quickly than when death 
has taken place slowly. 



74 RETROGRESSIVE PROCESSES 

Decomposition is the infallible sign. Its appearance de- 
pends upon the surrounding temperature, taking place more 
quickly in hot weather. It is first noticed as a greenish dis- 
coloration of the abdominal wall, and is due to the sulphuretted 
hydrogen from the intestines acting upon the iron contained 
within the hemoglobin. 

The tissues soften and there is more or less odor, due to the 
formation of various gases. 

Loss of elasticity, relaxation of the sphincter muscles and 
loss of transparency of the cornea, and dilatation of the pupils 
complete the list. 

Apparent death may occur in hysteria, catalepsy, submer- 
sion, cholera, exposure to cold, and action of electricity. It 
is detected by the absence of the signs of true death. The 
tissues will appear reddish if a light is held behind them, blood 
will flow from a wound, moisture will collect on a mirror held 
in front of the face, and the muscles will react to electricity. 



CHAPTER V 

CELL DIVISION 

As a result of the tissue injury in disease, repair is brought 
about by cell multiplication or reproduction. The extent 
of this regeneration depends upon the degree of specializa- 
tion of the tissue. 

The Cell. — The adult cell consists primarily of a mass of 
protoplasm or cytoplasm surrounded by a limiting membrane 
called the cell wall, and containing a nucleus within which there 
may be a small body called the nucleolus. 

The cytoplasm, which is a semifluid substance, is divided 
into two portions — the spongio plasm, which consists of a very 
elastic and extensible framework, and the hyaloplasm, which is 
homogeneous and less active. 

Embedded in the cytoplasm are minute granules known 
as microsomes. These are most numerous toward the cen- 
ter of the cell; the peripheral zone, called exo plasm, not con- 
taining them. 

Foreign bodies and vacuolations may also be found within 
the cell. 

The arrangement of the constituents of the cytoplasm varies 
at different times. Frequently the spongioplasm is arranged 
as a distinct reticulum. This is, however, not permanent, and 
seems to depend upon the relative proportion of the hyaloplasm. 

The nucleus is confined by a distinct wall, the nuclear mem- 
brane, within which is the nuclear substance or karyomitome. 
This is divided into a framework of fibrils, the nuclear fibril, 
and an interfibrillar substance, the nuclear matrix. 

The fibrils consist of a part called chromatin or nuclein that 
has a marked affinity for nuclear stain. This portion is sup- 
ported by fine fibrils of I in in that do not stain. 

There is also present a semifluid substance known as the 
karyoplasm or nuclear juice. 

75 



7 6 



CELL DIVISION 



The nucleolus lies within the nucleus and consists of a sub- 
stance known as pyrenin. Just what is its function is not known. 
It probably has a distinct purpose during cell multiplication, as 
it disappears during the division of the nucleus, but reappears 
when the new nucleus is formed. 

Another body, the centrosome, is also sometimes found. It is 
a small, highly refracting body, situated within the nucleus. 



Vacuoles. 



Chromatin network 




Nuclear membrane. 



Exoplasm, | 



Spongioplasm. 
Hyaloplasm. 

Nucleolus. 
Chromatin net-knot. 

Centrosome. 



fc Centrosphere. 



Foreign inclosures. Metaplasm. 



Fig. 14. — Diagram of a Cell (Huber). 

It is surrounded by a clear area called the attraction, sphere. 
This body, although it may be found during the stage of rest, 
becomes most noticeable during the stage of division of the 
nucleus. At that time it divides into two and passes to opposite 
poles of the cells. 

Occasionally a small irregularly spheric body, the para- 
nucleus, is present in the cytoplasm near the nucleus. Its 
function is not known. 



FUNCTIONS OF CELLS 77 

The relation between the size of the nucleus and that of 
the cell varies greatly. In certain cells, as in the lymphocyte, 
the nucleus may occupy nearly the entire area. 

The nuclei of the same kind of cells are usually similar in 
shape and size. They may be round, oval, or, as in some 
of the lower animals particularly, irregular. The shape of the 
cell depends partly on environment, partly on specialization. 

A cell may also have one or more nuclei, the latter being known 
as giant cells. 

With the exception of the red blood-corpuscles and the 
horny layer of the skin, all cells under normal conditions con- 
tain nuclei. The absence of a nucleus, therefore, usually denotes 
the loss of cellular activity. 

The functions of cells which distinguish living from inor- 
ganic tissues can be divided into: 

i. Metabolism, the power of selecting and assimilating 
food, anabolism; and the power of casting off excrementitious 
matter, catabolism. 

2. Growth, the result of assimilation producing an increase in 
the size of the cell. 

3. Irritability, response of the living cell to external influences. 

4. Motion, which may be of three different kinds. There 
is a constant passage of a "circulating albumin" from one part of 
the cell to another. It may be ameboid, so called on account of 
its resemblance to the motion of the ameba. It consists of 
a streaming of the cytoplasm to one point, giving rise to pro- 
longations or psendopodia extending from the surface of the cell. 

Ciliary movement is the result of the presence on the sur- 
face of cells of minute, hair-like processes, called cilia. These 
are prolongations and specializations of the protoplasm. The 
cilia keep up a movement like that of a whip-lash, always in 
the same direction. 

5. Reproduction is the multiplication of a cell, and may take 
place in one of two ways, either by direct division, amitosis, 
which is not the common method, or by indirect division, 
karyokinesis, karyomitosis, or mitosis. The latter is the more 
usual way. 

In amitosis or direct division there is first noticed a slight 



78 CELL DIVISION 

contraction in the nucleus of the cell. This gradually goes on 
until two new nuclei are formed. During this period the cyto- 
plasm begins dividing, and by the time the nuclei have migrated 
to opposite poles, separation has taken place and two new cells 
have formed. 

If the cytoplasm fails to divide, multinuclear or giant cells 
may arise. 

Karyokinesis. — In karyokinesis, or indirect division, the 
cell goes through a very complicated course of changes of the 
various elements, probably the result of definite metabolic 
processes. 

The changes can best be considered under four headings : 

1. The Prophase. — The centrosome increases in size, passes 
from the nucleus into the cytoplasm, and divides into two. 

Surrounding each centrosome is a mass of fine radiating 
lines known as the amphiaster. The rays extending from 
one centrosome to another are arranged in spindle form, the 
centrosomes being situated at the apices of the spindles. These 
achromatin rays form the nuclear spindle. 

The nucleus has been enlarging and the chromatin increas- 
ing, its particles uniting to form a long fuzzy thread. These 
fibrils become tangled and convoluted and form the close skein. 
The fibrils become thicker, less convoluted, and arrange them- 
selves in irregular loops, forming the loose skein. The chromatin 
now stains much more deeply than normally. These loops 
finally separate at their peripheral ends and form the chromo- 
somes, V-shaped fibrils with their closed ends arranged in a clear 
space known as the polar field. 

During the formation of the skeins the nucleolus and the 
nuclear membrane disappear and the chromatin fibrils lie in the 
cell protoplasm. 

The chromosomes are always present in the same number in 
the same species, varying from 2 to 50 in various animals; in 
man being 24. 

The arrangement of the fibrils about the polar field con- 
stitutes the mother star or monaster. 

2. The Metaphase. — Each of the chromosomes undergoes 
a longitudinal division into two. These filaments, with the 



KARYOKINESIS 



79 



closed end advancing, begin to separate, moving toward their 
respective poles or centrosomes. 




Fig. 15. — Nuclear Changes in Karyokinesis (Hatschek). 
a, Nucleus of spermatoblast of Salamandra maculata, with chromatin 
threads forming the first suggestion of a coil; b, close coil with disappear- 
ance of the fuzzy aspect and longitudinal cleavage of the threads. 





Fig. 16. — Diagrammatic Appear- Fig. 17. — Diagrammatic Repre- 
ance of the relation of the sentation of the nuclear 

Chromosomes to the Centro- Spindle and of the Ar- 

somes and Primitive Nuclear rangement of the Double 

Spindle (Flemming). Chromosomes ln an Equa- 

torial Plane Preparatory 
to Separation. This Stage 
is Called the Mother Star 
(Flemming) . 

3. The anaphase begins with the migration of the chro- 
mosomes. As they move toward the opposite poles the free 
ends constitute the equatorial plate. Connecting the ends are 
fine threads of achromatin known as the connecting filaments. 



8o 



CELL DIVISION 



The chromosomes collect at the opposite ends and form the 
daughter stars or diasters. As this occurs there is the beginning 
of a constriction of the protoplasm. 





Fig. i 8. — Diagrammatic Representation of the Separation of the 
Chromosomes, which are Attached toward Opposite Poles of 
the Nuclear Spindle, about which They Gather to Form the 
"Daughter Stars" (Flemming) . 

4. The Telophase. — The constriction continues until the 
original cell has been completely divided and two new ones 
formed. The chromosomes now undergo in reverse order the 




Fig. 19. — Segmentation of the Cytoplasm, and the Chromosomes 
Equally Divided, about to Form New Nuclei in the New Cells 
(Flemming). 

phases that have been described: the loose skein, the close skein, 
the reappearance of the nuclear membrane and of the nucleolus, 
with finally the stage of rest. 



KARYOKINESIS 8 1 

To summarize, the changes are as follows: 
Resting mother nucleus. 
Prophase. 

Migration and division of the centrosome with 

increase of chromatin. 
Close skein. 

Disappearance of the nuclear membrane. 
Disappearance of the nucleolus. 
Loose skein. 

Separation of the skein into chromosomes. 
Appearance of the polar field. 
Rearrangement of the chromosomes around polar 

field. 
Monaster, or mother star. 
Appearance of the nuclear spindle. 
Metaphase. 

Longitudinal division of the chromosomes. 
Anaphase. 

Migration of the divided chromosomes to op- 
posite ends of the cell. 
Formation of the equatorial plate. 
Diaster or daughter star. 
Telophase. 

Constriction of the protoplasm. 

Daughter skeins undergoing in reverse order the 

above changes. 
The stage of rest. 
In some instances, instead of the cytoplasm dividing when 
cleavage of the nucleus is completed, it remains unchanged. 
This may go on until there are many nuclei, imbedded within 
a single mass of cytoplasm. Such formations are known as 
giant cells, and may be the result of division under unfavorable 
circumstances. 

There may be the formation of more than two centrosomes 
with a resulting multipolar cell. The equatorial segments may 
split up more than once and the daughter cells may divide 
secondarily. 



CHAPTER VI 

INFLAMMATION AND REGENERATION 

Inflammation is the protective reaction of irritated and 
damaged tissues which still retain vitality. 

Etiology. — The causes of inflammation may be divided into 
mechanical, chemical, and vital, or infectious and non-infectious. 

Traumatism of any nature, such as a blow or the action 
of chemicals, can give rise to an inflammatory reaction and 
be non-infectious. 

The common cause, however, is the action of bacteria upon 
the tissues. The great majority, therefore, of inflammations 
are infectious or vital in variety. 

A non-infectious one may become infectious through a 
secondary deposit of bacteria. 

An infectious inflammation is distinguished by the fact that 
it is likely to be progressive, is capable of indefinite increase, 
and may also be transmitted from one individual to another. 

Before taking up the pathologic changes of the circulation 
it will be necessary to first consider the normal differences in 
the blood-current in arteries, veins, and capillaries. 

In arteries the stream is not constant; it is regularly inter- 
mittent on account of the rhythmic contractions of the heart. 
It is more rapid than in the veins; the red cells cannot be dis- 
tinguished at the height of systole, but at the end of the heart's 
action the current slows sufficiently for them to be seen. The 
corpuscles occupy the entire lumen, except that at the end of the 
pulse-wave they momentarily withdraw from the wall of the 
blood-vessel. 

In veins the stream is constant and is regular in speed. In- 
stead of cells and plasma being uniformly mixed there are 
two zones present: an axial or central zone, composed of blood- 
82 



CIRCULATORY CHANGES 



83 



cells, and a peripheral one, made up of the blood-plasma. In 
this latter there are occasionally a few leukocytes, but no ery- 
throcytes found. 

In capillaries the current is 
neither constant nor regularly 
intermittent. It is constant 
during the flow. 

The changes in the circulation 
in inflammation are as follows: 

1. A momentary contraction 
of the blood-vessel following the 
introduction of the irritant. 
This is followed by: 

2. A marked dilatation and 
relaxation of the vessel with at 
first an increase in the rapidity of 
the flow. Arterioles are first af- 
fected, then veins and capillaries. 

3. Further increase in dilatation with slowing of the cur- 
rent. Instead of the cells being unrecognizable in the arteries, 




Fig. 20. — Acute Inflammation 
(Mallory). 

Peripheral arrangement of 
polymorphonuclear leukocytes in 
vein. 




Fig. 21. — Inflammation of the Mesentery, Showing Overfilling of 
the Blood-vessels, with Emigration of Leukocytes and Dia- 
pedesis of Red Corpuscles (Ziegler). 

they now become distinctly visible. Marked changes now 
occur, particularly in the venous circulation. The plasmatic 



84 



INFLAMMATION AND REGENERATION 




:?° :*& * "*• 'J 






zone, which at first contained only a few leukocytes, shows an 
increase in their number until it is entirely filled with them. 
Subsequent to this there takes place 
an exudation of fluid and blood-cells 
from the vessels. 

Emigration or Transmigration of 
the Leukocytes. — At first the leuko- 
cytes adhere but slightly to the walls 
of the blood-vessel, assuming a pear 
shape, the enlarged ends pointing in 
the direction of the current. In the 
course of five or six hours all the 
small veins of the involved area may 
show a mass of leukocytes along their 
walls. These in time become closely at- 
tached, pass through the vessel walls, 
and, finally, may become pus cells. 

As a rule, the greater number of 
leukocytes that escape are of the 
polymorphonuclear variety. They 
project a small mass of protoplasm 
through the vessel wall. This mass 
becomes gradually larger until the 
cell lies outside in the surrounding 
tissues. This process is known as 
emigration. 

Diapedesis refers to the escape of 
red cells from vessels whose walls 
show no lesions. 

At the same time that the cells 
escape there is an exudation or out- 
flow of lymph through the vessel 
walls. This increased amount of 
lymph renders the tissue edematous 
and gives room for free ameboid 
movement of the leukocytes. Many 
are actively phagocytic, many die, while some get back into 
the lymph-vessels and return to the general circulation. 







Fig. 22. — Acute Inflam- 
mation (Mallory). 
Emigration and ac- 
cumulation of polymorpho- 
nuclear leukocytes in the 
subcutaneous tissues of a 
rabbit's ear as the result of 
rubbing the surface with 
dilute croton oil. 



CARDINAL SYMPTOMS 85 

As to the emigration of the leukocytes there are various 
theories, but the reasons are not perfectly understood. The 
phenomena can hardly be due to nervous influences, as the 
changes occur too slowly. It is also impossible to bring about 
an inflammatory reaction by stimulating either the vaso- 
constrictors or the vasodilators. When the latter is done, 
there is an exudation of plasma, but not of cells. According to 
Cohnheim, there is an increased permeability of the blood- 
vessel wall due to structural changes. 

Probably the chief reason is that the ameboid motion of 
the leukocytes is very much stimulated. 

It may also be the result of positive chemotaxis, the attrac- 
tion that certain substances exert upon motile cells. Dead 
tissues and the products of bacterial growth are positively 
chemo tactic, and their influence may be exerted upon the 
leukocytes while they are still within the blood-vessel. 

Besides the polymorphonuclear leukocyte the round mono- 
nuclear form may also escape, giving rise to the round-cell 
infiltration that is found in subacute or chronic inflammation, 
particularly in tuberculosis and syphilis. 

As a result of the disturbances of the circulation there are 
certain changes in the inflamed part as a whole that are fre- 
quently spoken of as the cardinal symptoms of inflammation: 

Pain, or dolor, due probably to the pressure exerted upon 
the terminal nerve-filaments. Also to the action of toxins, 
acids, enzymes, etc., upon the nerve-endings. 

Swelling, or tumor, due to the increased amount of blood 
present and to the exudate within the tissues. 

Redness, or rubor, due also to the hyperemia. The increase 
of blood to the involved part brings more leukocytes, diluents, 
and antibodies, facilitates the removal of harmful substances, 
and possibly, in some instances, affords increased nutrition to 
the cells in that area. 

Heat, or calor, the result of two causes, one that more blood 
is brought to the part, the other that the blood moves more 
slowly and heat accumulates. 

Altered function, or functio laeso, may be added to the first 
four. 



86 



INFLAMMATION AND REGENERATION 




Fig. 23. — Ileum; Typpioid 
Fever (Early Stage) 
(Nicholls). 
Peyer'spatchesandsoli- 

tary follicles greatly swollen; 

superficial ulceration. 



The products of inflammation are 
known as inflammatory exudates. 

A serous exudate is one that is 
composed of fluid that has escaped 
from the vessels. It contains few 
cells, occurs in very slight inflamma- 
tions, and tends to coagulate spon- 
taneously. 

This fluid differs from the non- 
inflammatory transudate in contain- 
ing a greater amount "of albumin, 
and, therefore, being of a greater 
specific gravity. The amount of exu- 
date depends largely upon the vascu- 
larity of the part. 

A fibrinous exudate is one in which 
there is more or less fibrin present, 
which probably helps restrict the es- 
cape of the infecting agents. It is 
formed by the action of fibrin ferment 
acting upon fibrinogen or fibrin-form- 
ing substances in the presence of cal- 
cium salts. This ferment is yielded 
probably to some extent by all the 
cells of the blood, but particularly 
by the leukocytes. When they die, 
the ferment is formed and the fibrino- 
gen is converted into fibrin. When 
the leukocytes are increased in num- 
ber, the amount of fibrin is usually 
greater. 

A purulent exudate is one in which 
there is a preponderance of escaped 
leukocytes. It may be found infil- 
trating the tissues or in a circum- 
scribed area known as an abscess. 
This exudate is known as pus. 

A hemorrhagic exudation is one 



INFLAMMATORY EXUDATES 



87 



that contains erythrocytes. It generally indicates that there 
has been a lesion of blood-vessels. 

Pus is an opaque, yellowish, alkaline fluid, specific gravity 
about 1050. It is made up of pus cells, either living or dead 
polymorphonuclear leukocytes, and pus serum (liquor puris). 
Usually some degenerated tissue cells are present. According 
to whether there is blood, serum, or mucus as well, it may be 
sanious pus, seropus, or mucopus. 

If the fluid portion is scanty, the pus may be creamy or 
cheesy; or ichorous if the pus is very thin, watery, and acrid. 




Fig. 24. — Tuberculous Ulceration of the Intestine (Stengel). 



An abscess is a circumscribed collection of pus. It is sur- 
rounded by an inflammatory zone incorrectly called a pyogenic 
membrane. 

An abscess may be hot or cold. The first is the result of 
acute inflammatory changes. The latter is a chronic inflam- 
matory process, and the fluid contained within it is not pus, but 
is made up of broken-down and degenerated tissues. 

An embolic abscess is one that has followed the lodgment 
of a septic embolus. 

Pyemic or metastatic abscesses are those resulting from pyo- 



88 



INFLAMMATION AND REGENERATION 



genie organisms present in the blood becoming lodged in the 
tissues and causing local purulent lesions. 

The various steps occurring in the formation of an abscess 
due to bacterial infection are as follows : After the pus-producing 
organisms gain entrance they undergo multiplication without 
at first causing any reaction. In a very short time, however, 
the invaded area becomes congested, the leukocytes approach 
the wall of the blood-vessels, and degenerative changes in the 
neighboring tissue cells appear. There is a multiplication of 
the bacteria, the polymorphonuclear leukocytes escape from 
the vessels, and mononuclear leukocytes (small round cells) 
collect. The polynuclear leukocytes and other cells, including 




Fig. 25. — Chronic Ulcer op the Stomach. Showing a Section Through 
the Stomach Wall at the Central Part of the Round Ulcer 
(Delafield and Prudden). 



endothelial cells, take up large numbers of bacteria. More 
leukocytes appear until the tissue becomes densely filled by 
them. This is accompanied by a yet greater proliferation of 
the bacteria which extend along the lymph-streams into the 
region outside of the developing abscess. There is now a break- 
ing down of the leukocytes, with the setting free of various fer- 
ments and a coincident destruction of the tissue of the affected 
portion. 

The destruction of tissue that accompanies abscess forma- 
tion is in consequence of there being an insufficient amount 
of nutrition, and is due also to the dissolving effect of digestive 



TERMINATION OF INFLAMMATION 89 

enzymes present in the liquor puris, probably derived from the 
broken-down leukocytes. 

When the broken-down tissue has been cast off there remains 
a superficial lesion with loss of substance. This area is known 
as an ulcer. 

A sinus is an inflammatory tract that is open at one end 
from which the exudate can escape. 

A fistula is an inflammatory tract that is open at both ends. 
It is one that joins an internal cavity to the surface. 

The termination of inflammation depends upon the degree 
of inflammation and the amount of damage done. It may 
occur by resolution. This takes place only when the inflam- 
mation has been slight. The exudate is taken up by the 
lymphatics and returned to the circulation. Any degenerated 
cells will be taken up by the wandering leukocytes and the 
tissue will resume its normal condition. 

In suppuration the inflammation has been destructive; 
there is actual loss of tissue, with the formation of pus. 

As pus is formed it is either confined as an abscess or else 
it tends to infiltrate the tissues. In either case the tissues at- 
tempt to get rid of the irritating substance by having it fol- 
low along the least resistant paths and letting it escape from 
the body. This process of extension is known as "burrowing"; 
it results from the increased pressure due to the presence of 
the pus and to the digestive powers of the enzymes contained 
within. 

In some cases the pus may quickly escape to the surface 
of the body and be cast off. It may, however, have to bur- 
row a long distance, as in a psoas abscess, before it can escape. 

Sometimes the pus may gain entrance into one of the cav- 
ities of the body, as the peritoneum or pleura, and give rise 
to inflammatory conditions there. 

According to the cavity involved, the condition has special 
names. Empyema is pus within a pleural cavity; pyoperi- 
cardium when within the pericardial sac; pyosalpinx when 
a Fallopian tube is involved, etc. 

Encapsulation is what takes place when the irritating mate- 
rial cannot be removed from the body. The surrounding 



90 INFLAMMATION AND REGENERATION 

tissue cells undergo multiplication and the substance is isolated 
by the formation of a connective-tissue capsule about it. 

Organization is the process of repair by means of which 
the destroyed areas are filled up by connective tissue. It is 
not a case of the transformation of the inflammatory prod- 
ucts into connective tissue, but is a condition of replacing. 
This new formation of connective tissue is known as a cica- 
trix or scar, the process as cicatrization. 

The cells present in the repair of inflammation are derived 
from various sources, and consequently differ among them- 
selves. 

The leukocytes that form the greatest numbers are derived 
from the blood and are chiefly of the polymorphonuclear 
variety. 

Lymphocytes both large and small, as well as eosinophiles 
in small numbers, may also be present. 

Eosinophile cells are actively ameboid and are able to escape 
from the blood-vessels. As a rule, they are not present in 
marked numbers except in certain subacute or chronic inflam- 
mations of the skin or mucous membranes. 

The plasma cells probably originate from the connective 
tissue, but may be derived partly from the blood. They are 
rather large, and contain a pale, vesicular nucleus eccentrically 
placed and a finely granular basophilic protoplasm. These 
cells are usually most numerous in acute toxic conditions and 
are supposed to play some part in the formation of connective 
tissue. 

The mast cells or basophilic leukocytes are large cells containing 
usually a trilobed vesicular nucleus and large granules in the 
cytoplasm. They are most common in inflammations of mu- 
cous membranes and in the neighborhood of tumors, especially 
if they have undergone mucoid changes. 

The fibroblasts or epithelioid cells are formed by the pro- 
liferation of pre-existing connective- tissue cells. 

Giant cells, those containing more than one nucleus, are 
frequently present. The formation of these cells probably 
takes place in one of two ways. If a single cell is not suffi- 
ciently powerful to remove the offending particle, several 



TERMINATION OF INFLAMMATION 



9 1 



may coalesce, and in that way successfully make the attack. 
They may, however, form through a multiplication of the nuclei 
without division of the cytoplasm. 

In the process of repair there is formed what is called granu- 
lation tissue which acts as a strong barrier to absorption and 
infection. In it there is the formation of loops of new capillaries 




Fig. 26. — Granulation Tissue (Mallory). 
a, Surface portion, composed chiefly of newly formed blood-vessels; 
very few fibroblasts; many polymorphonuclear leukocytes between the 
vessels and in the fibrin on the surface; blood-vessels and leukocytes sepa- 
rated by serum, b, Deeper portion; many lymphocytes between blood- 
vessels; young fibroblasts growing in horizontal arrangement at base. 



derived from the endothelial lining of pre-existing blood-vessels. 
The endothelial cell becomes larger, the nucleus divides by 
mitosis, and two cells are formed. These cells continue dividing 
until a sprout-like process extending into the surrounding tissue 
is formed. Adjoining sprouts unite, and, although at first solid, 
finally become hollowed out, thus allowing the circulation to be 



92 INFLAMMATION AND REGENERATION 

re-established. At the same time that this is taking place there 
is a multiplication of the fixed connective-tissue cells, which 
surround and act as a supporting framework to the loops of 
new-forming capillaries. 

In the proliferation of the connective tissue there is first 
found a small round cell with a round or oval nucleus. As 
the tissue becomes older the cells tend to elongate and be- 
come spindle shaped. At first they are very close together, but 
gradually separate, and the homogeneous intercellular sub- 
stance becomes fibrillar and supports the cells. Those cells 
concerned in the formation of the cicatrix are called fibroblasts. 

In the new-formed tissue there is at first an overproduction 
of cells and blood-vessels, but eventually it becomes less vas- 
cular and cellular. This is brought about to a great extent by 
the contraction of the cicatrix, which, at first reddish and 
elevated, finally becomes pale and depressed. 

According to surgeons, cicatrization may take place in one of 
two ways: 

Union by first intention, or primary union. In this the edges 
of the wound are closely brought together and very little exudate 
escapes. In this narrow space the same processes take place as 
are seen in the formation of granulation tissue, coagulation, 
fibrin formation, phagocytosis, and proliferation of capillaries 
and connective tissue, but to a much less extent. The epithelial 
surface is replaced by a proliferation of the neighboring epithe- 
lium. 

Union by second intention, secondary union, or union by 
granulation, takes place when the edges of the wound are far 
apart and there is a large amount of exudate present. 

This process is the same as healing by first intention, except 
that in it there is supplied the material bridge over the gap. 

If an epithelial surface is affected, the granulation tissue is 
gradually covered by proliferation of adjacent cells. 

Regeneration, although commonly applied to the forma- 
tion of cicatricial tissue, really refers to the power of indi- 
vidual tissues to reproduce their own kind. 

Generally speaking, the more highly specialized the tis- 
sue, the less is its regenerative power. If such tissues are 



TERMINATION OF INFLAMMATION 



93 



destroyed, they are generally replaced by fibrous tissue. A 
cell can give rise in regeneration only to a tissue that has the 
same blastodermic origin. 

The fibrous connective tissue is probably the most active. 

Epithelium of the surface variety is constantly and com- 
pletely regenerating. Whether regeneration takes place in 







Fig. 27. — Heart. Organizing Pericarditis. Fibrin still Present 
Along Surface and Beneath it (Mallory). 



the more highly specialized epithelial organs, such as the 
kidney and liver, is rather improbable. 

Muscular tissue is capable of regeneration to a slight degree, 
but the chief repair after injury to muscle takes place within 
the connective tissues surrounding the fibers. 

Blood-vessels, as is seen in the formation of granulation tis- 
sue, are capable of marked multiplication. The new-formed 



94 INFLAMMATION AND REGENERATION 

vessels in regeneration are usually only temporary; existing 
only long enough for the tissue to receive its nutrition, then 
disappearing during the contraction of the cicatrix. 

Bone, as is noticed in the repair of fractures, is able to undergo 
complete regeneration. 

Cartilage is incapable of regeneration. In injuries it is re- 
placed by fibrous connective tissue. 

Nerve-cells of the highly specialized type, such as ganglion 
cells, cannot regenerate, but the neuroglia or nerve connective 
tissue can. The neuroglia differs from the ordinary fibrous 
tissue in that it is derived from the ectodermic layer of the blas- 
toderm. 

Varieties of Inflammation. — Inflammation may be — 

Acute when it arises rapidly, lasts a short time, and de- 
stroys tissue. 

Chronic when arising slowly, lasting a long time, and giving 
rise to the formation of fibrous connective tissue. 

Infectious when caused by some living organism. 

Non-infectious when it does not arise from the action of a 
living organism. 

Exudative if the inflammation is characterized by the pres- 
ence of an exudate. According to the variety of the exu- 
date, the inflammation may be as follows: 

Serous when the exudate consists of a fluid having few cell- 
ular contents. 

Fibrinous when particles of fibrin are present in the exu- 
date. 

Purulent when pus cells (leukocytes) are present in large 
numbers. 

Hemorrhagic when erythrocytes escape in quantity. 

Parenchymatous when the actively secreting cells of a gland- 
ular organ are involved. 

Interstitial if the inflammatory process involves the con- 
nective-tissue framework of an organ. 

Catarrhal when limited to mucous membranes. 

In the early stage the secretion of mucus by the cells ceases, 
the surface becomes dry, and the blood-vessels congested. 
Later on, the secretion is increased in amount, frequently 



VARIETIES OF INFLAMMATION 95 

changed in character, and the congestion of the vessels some- 
what lessened. 

Desquamative if there is a casting off of epithelium in a ca- 
tarrhal inflammation. 

Vesicular when there are larger and smaller circumscribed 
elevated areas containing a serous exudate, as in blisters. 

Pustular when the circumscribed elevations contain pus. 

Diphtheric or croupous when there is a marked coagu- 
lation of fibrin on the surface with the formation of a pseudo- 
membrane in which are found degenerated cells of various 
types — epithelial, leukocytes, and erythrocytes. 

In it there is usually necrosis involving the superficial epi- 
thelium, or going deeper and attacking the submucosa as well 
as the mucosa. 

Ulcerative if accompanied by a loss of superficial substance. 

Degenerative w r hen the destruction of tissue is extensive. 

Adhesive when, as the result of the presence of fibrin, replace- 
ment by fibrous tissue follows and the two opposing surfaces 
become more or less adherent, the process being the same as 
occurs in scar formation. It may go on to the point where the 
cavity entirely disappears, and is then called oblitcrative. 

Gangrenous when there has been infection of the tissues 
by putrefying, saprophytic organisms and gangrene is present. 

Phlegmonous when the interstitial tissues become infiltrated 
by pus. 

Productive when the formation of fibrous connective tissue 
is prominent. 

Specific when caused by a definite micro-organism. 



CHAPTER VII 
THE SPECIFIC INFLAMMATIONS (GRANULOMATA) 

TUBERCULOSIS 

Tuberculosis is a specific infectious disease characterized by 
the formation of tubercles. 

It is caused by the Bacillus tuberculosis, which is non-motile, 
non-sporogenous, aerobic, acid resisting, and purely parasitic. 
Occurs as a slender, rod-shaped, slightly curved body, usually 
with rounded ends, but sometimes showing distinct branches. 
It is about 1.5 to 3.5 ^ long by 0.25 fi wide. It is found in 
sputa and in the lesion of tuberculosis. It is the cause of all 
forms of tuberculosis in man and may be transmitted to many 
of the lower animals. It is still unsettled whether the forms 
found in animals are capable of being pathogenic to man. 
The bovine bacillus, however, is apparently pathogenic in a 
small percentage of cases. 

Staining is difficult, but after having once taken it up, the 
organism is with difficulty decolorized. Use Ziehl-Neelson 
method. Stains by Gram's. 

Culture. — Blood-serum, glycerin agar-agar, potato, and glyc- 
erin bouillon. It is difficult to cultivate, growth is slow, best 
at 37 C, none when below 29 C. or above 42 C. Growth 
is dry, lusterless, coarsely granular, wrinkled, and slightly 
yellowish. 

Pathogenesis. — Tuberculosis results from the successful 
invasion of the Bacillus tuberculosis. This may take place 
by means of: (1) the respiration; (2) the blood circulation; 
(3) lymphatic channels; (4) ingestion. After having gained 
entrance it may give metastases by any of the first three, by 
continuity of tissue, or by direct implantation. 

The characteristic lesion is the miliary tubercle, which is 
gray in color as long as degeneration and caseation have not 
96 



PATHOGENESIS 97 

occurred; it then becomes yellow. It is rarely circumscribed 
by any definite boundary, and it tends to infiltrate and form 
tubercles in the adjacent tissues. It is a small area of inflam- 
mation and degeneration resulting from the action of the 
bacillus. The primary lesion does not necessarily occur at the 
point where the bacilli gained entrance. When the organism 
enters a suitable location, it undergoes multiplication. In a 
short time their number and the products of their metabolism 
bring about an increase in the number of fixed connective-tissue 
cells — epithelioid cells. These cells are the first to appear. A 
little later, through the chemotactic effect of the bacteria, 
lymphoid cells escape from the blood-vessels. According to 
which cell predominates, the tubercle may be either epithelioid 
or lymphoid. 

As the bacteria multiply, more nutrition is required, but 
this variety of inflammation is peculiar in that not only no 
new blood-vessels are formed, but the pre-existing ones are 
destroyed by endarteritis and thrombosis as the process ad- 
vances. Consequently, the central area, the older portion, 
undergoes degeneration and coagulation necrosis. 

The tubercle may be divided into three zones, according to its 
histologic characteristics: (i) A central zone containing bacteria 
and tissue cells that have undergone coagulation necrosis. (2) 
A median zone, in which are many epithelioid cells and frequently 
giant cells containing vesicular nuclei arranged peripherally 
and radially. (3) A peripheral zone, in which are found a few 
epithelioid, many lymphoid, and some plasma cells. 

The giant cells as well as the epithelioid may come from 
the endothelium of the blood-vessels or lymph- vessels, from 
fibroblasts or from escaped leukocytes. 

If the process has been rapid, the lymphoid cells usually 
predominate, [f the individual's resistance is fairly good, some 
of the epithelioid cells may be converted into fibrous tissue. 
When resistance is marked, the tubercle may become encap- 
sulated by fibrous tissue, and eventually become infiltrated by 
lime salts. This occurs only where the resisting power of the 
patient becomes greater than the destroying ability of the 
organism. 
7 



98 THE SPECIFIC INFLAMMATIONS (GRANULOMATA) 

As, however, the bacilli keep continually multiplying, the 
tendency of the disease is to extend. This occurs by the organ- 
isms being carried into the lymphatic channels either directly 
or by the action of phagocytes. The latter may carry and 
deposit them in a neighboring lymph-node, where secondary 
lesions will occur. Metastasis may also take place by the 
organisms gaining entrance into a vein, entering the general 



Wy' : ' 


# :" 








^•v. , 


X ,=*>■,£ • 


' 


v^^/i 




■ >_ j 


**v 


if— >!» 


^' ' 




"V""' 











Fig. 28. — Subacute Tuberculosis of a Lymph-gland. X 70 (Diirck). 
1, Thickened capsule; 2, caseous centers of the tubercles. At the 
periphery of the gland the tubercles are still discrete, and between them 
lies lymphadenoid tissue. In the center of the gland the nodules have 
formed larger confluent areas. Numerous giant cells. 

circulation, and setting up a more or less widely diffused general 
miliary infection. 

Recovery from tuberculosis is more common than is generally 
believed. According to postmortem examinations, 20 per cent, 
of the cases of tuberculosis recover. In such cases there is 
present the ability of the individual to resist the inroads of the 
process. The tubercle bacilli become encapsulated in a mass 
of connective tissue that prevents their further growth and 



LEPROSY 99 

extension. This new-formed tissue tends to contract and causes 
the broken-down portions to be absorbed, or else calcareous 
infiltration takes place. 

These walled-off areas are, however, still a source of danger. 
Although tubercle bacilli do not form spores, yet infection may 
take place years after the connective-tissue growth, if for any 
reason the contents happen to escape. 

When it remains quiet it is called "latent" tuberculosis. 

The symptoms seen are probably due in a great part to the 
presence of associated pyogenic organisms. The night-sweats, 
fever, and loss of weight seen in cases of pulmonary tuberculosis 
are due to the associated bacteria. There is generally present 
some anemia, and many authors claim that there is an increase 
in the number of lymphocytes in the blood. 

The liver frequently shows marked fatty infiltration and some- 
times amyloid degeneration to a slight or a marked degree, de- 
pending upon the amount of suppuration. 

The most common entrance for infection is the respiratory 
system. Sputum from tuberculous patients becomes dried and 
comminuted ; it is then carried about by the currents of air and 
enters the body. 

The intestines may become secondarily involved through 
infection brought about by swallowing the tuberculous sputum. 

Congenital tuberculosis may come from the paternal side 
from infection of the genitals ; from the maternal side through 
infection of an ovum, or it may be transmitted through the 
placenta. Heredity is no longer thought to have much direct 
influence. It is now believed that what is inherited is nothing 
more than a weakened resisting power. 

LEPROSY 

Leprosy is a chronic, specific, infectious, inflammatory dis- 
ease caused by the Bacillus leprae, which is a non-motile, non- 
sporogenous, acid-resisting, purely parasitic organism. It is 
pathogenic for man, but some of the lower animals appear to be 
somewhat susceptible. Is very slightly contagious. Is stained 
with some difficulty. Stains by Gram's. An acid-fast organism 



IOO THE SPECIFIC INFLAMMATIONS (GRANULOMATA) 

supposed to be the B. leprae has been grown on artificial culture- 
media containing split-up nucleoproteins. 

It occurs most commonly in warm climates and in people 
of almost any age. Is most common in males of from twenty 
to thirty years. It is probably not hereditary, but children 
under three years have been affected. Infection may be trans- 



f 


! 


/ s 1 " '-« 


;'_'" 


t . 


3H| 


1 


"* "CV^i 



Fig. 29. — Nodular Leprosy. 



mitted by: (1) direct inoculation; (2) kissing and sexual inter- 
course; (3) clothing; (4) bites of insects. 

The bacilli are distributed to an extraordinary extent in 
the body of the leper, and in many cases there will be no in- 
flammatory reaction in their neighborhood. They may be 
either extracellular or intracellular, and in the latter case may 
be found in giant cells or lepra cells. These may contain numer- 
ous nuclei and numbers of vacuoles as well as bacteria. 



VARIETIES OF LEPROSY 



IOI 



The secretions of the numerous membranes of the nose usually 
contain great numbers of the bacilli. 

Varieties. — Two forms are commonly met with, the nodular 
and the anesthetic or nerve leprosy. It is seldom, however, that 
a quite pure case of either is found; the majority belong to the 
mixed form. In the nodular variety the node may be preceded 




\ 




Fig. 30. — Macular Lesions in Anesthetic Leprosy. 



by a hyperemic patch which leaves behind it a pigmented area. 
The nodules appear first in the skin and subcutaneous tissue of 
the face, and may remain single or become confluent. 

Macroscopically the nodes are rather grayish or yellowish. 
Microscopically each node is made up of granulomatous tissue 
composed of lymphoid and epithelioid cells retained in a loose 



102 THE SPECIFIC INFLAMMATIONS (GRANULOMATA) 

connective- tissue network; in these masses the bacilli occur in 
great number between and in the cells. These lesions are more 
vascular than those of tuberculosis, and consequently do not 
tend to undergo coagulation necrosis. Caseation does not take 
place and the ulceration that is so common depends largely upon 
injuries and secondary infections. 

The nodules are found in other parts of the body, as on the 
back of the hand, — palm is not usually involved, — in the mucous 
membrane of the eye, nose, mouth, larynx, and intestines. 

The lymph-glands in both varieties are swollen, hard from 
connective-tissue formation, and yellowish on account of fatty 
degeneration. 

Anesthetic leprosy is characterized by the growth of the 
bacilli in the sheath of the nerves and an increase in the con- 
nective tissue along their course. Is most common on the 
ulnar and popliteal nerves, which at first may be painful. 
There then appears neuritis with localized hyperemic spots, 
the nerve affected being red and swollen; later it becomes 
harder, pale, and gray, with nodular or fusiform enlargements. 
The neurilemma usually becomes thickened, fibrous, and infil- 
trated by cells and bacilli. These become anesthetic, and in 
some cases become the seat of a blister. Finally, ulceration 
may develop with the subsequent loss of the fingers or toes. 

Many of the enlarged nodes may be the result of a sec- 
ondary tuberculosis occurring late in the course of the disease. 
There is frequently fever and also nephritis. Amyloid degen- 
eration is not uncommon in the ulcerative forms. 

The majority of the cases last from five to twenty years, 
usually dying of tuberculosis. 

GLANDERS 

Is a specific infectious disease of horses that is sometimes 
seen in man as the result of accidental infection. 

Is caused by the Bacillus mallei, a non-motile, non-spor- 
ulating, aerobic or optionally anaerobic bacillus 2 to 5 (A in 
length. Is pathogenic for man and lower animals. Stains by 
ordinary methods, but not by Gram's. Grows on ordinary 
media, but best on glycerin agar. 



GLANDERS 103 

It makes its appearance in the membrane of the nose in 
horses in the form of small nodules the size of a pea. These 
may increase in size, but eventually break down and ulcerate, 
with the formation of irregular ulcers, having yellowish, ele- 
vated, and indurated borders from which some bloody pus is 
discharged. Lymph-nodes become enlarged, and metastatic 
abscesses may result. The lungs are frequently involved and 
macroscopically resemble a tuberculous bronchopneumonia. 









7*J V 









■if v 



Fig. 31. — Bacillus Mallei, from a Culture upon Glycerin Agar-agar. 
X 1000 (Frankel and Pfeiffer). 

Microscopically the nodules consist of masses of small round 
cells and epithelioid cells. Do not find giant cells. 

If the skin is involved the condition is known as ''farcy,'' 
and the nodules as "farcy buds." They generally undergo 
central necrosis and suppuration with very extensive ulcer- 
ation. 

Man may become infected through lesions of the mucous 
membranes of the eye or nose or of the skin, and the result 
is usually fatal. The course is that of an acute febrile affection 
suggesting typhoid fever. 



104 THE SPECIFIC INFLAMMATIONS (GRANULOMATA) 

SPOROTRICHOSIS 

Is a chronic inflammatory process due to the presence of a 
pathogenic fungus, formed of sporangia and mycelia, the sporo- 
trichium. These organisms are strictly aerobic; grow on the 
ordinary culture-media at a temperature of 20 to 28 C. They 
do not stain well, taking the ordinary anilin dyes faintly; if not 
decolorized too vigorously they stain by Gram's method. 

The lesion quite commonly starts at the site of some trifling 
injury, particularly of the hand. The infected area may or may 
not become sluggishly inflamed, and there develops a small 
dermic, sometimes subcutaneous, nodule which may break down 
and become soft. This may develop into a sluggishly inflamed, 
discharging sore. 

Sooner or later a subcutaneous nodule will be felt at the lower 
end of the forearm. This gradually enlarges to the size of a 
cherry, may spread laterally, and finally softens. The overlying 
skin becomes thinned and of a purplish color, then breaks through, 
the discharge being of a viscid, gelatinous, seropurulent charac- 
ter. This formation is successively followed by several such 
nodules higher up the arm along the lymphatic vessels which can 
be felt usually as hard cords. 

Microscopically may conform more or less closely to one of 
three types, or there may be an admixture of all varieties: 
1. Proliferation of the connective tissue with lymphoid cells, 
syphiloid. 2. Epithelioid proliferation with giant cells, tubercu- 
loid. 3. Polynuclear infiltration resembling suppuration. 

It may be difficult to find the organism by staining the dis- 
charges, but the fungus grows readily on ordinary culture-media. 

ACTINOMYCOSIS 

Is a chronic contagious disease of cattle, "lumpy jaw," 
but is sometimes found in man. 

Is caused by a fungus, probably a strep to thrix, the Actino- 
myces bovis, which is large enough to be seen by the naked eye, 
appearing as small yellow particles. The fungus is made up of a 
central mass of granular substance in which there are many 
structures resembling chains of cocci or spores. Extending 



ACTINOMYCOSIS 



I05 



-?♦■ 



from this center are many mycelial threads terminating in club- 
shaped extremities. Is both aerobic and anaerobic in its 
growth; was formerly thought that the latter form alone was 
pathogenic. Will grow on any artificial media. 

Stains yellow with picric acid, red with picrocarmin, blue with 
anilin gentian and by Gram's. 

The infection is supposed to take place by means of spores 
gaining entrance into the human system by means of food or by 
inhalation. Probably en- 
ters by way of decayed 
teeth or through abrasions 
of the mucous membrane. 

Where the fungus lodges 
there is a formation of 
nodules which break down, 
form abscesses, and dis- 
charge a creamy pus con- 
taining yellowish granules; 
which show the charac- 
teristic rayed appearance 
when looked at under the 
microscope. 

The neighboring bones 
may become riddled with 
sinuses and there may also 
be metastatic growths in 

other organs, particularly the lungs. In the latter extensive 
necrosis may occur, with the formation of small cavities con- 
taining pus and fragments of degenerated tissues, and the 
fungus will be found in the -sputum. 

Instead of breaking down, connective tissue may be formed 
and encapsulate the invaded area. 

Microscopically there is found a granulation tissue containing 
large masses of lymphoid cells, a few epithelioid cells, and giant 
cells resembling closely a tubercle. 




* 






Fig. 32. — Actinomyces Cluster Show- 
ing Radial Striations at Per- 
iphery (Karg and Schmorl). 



106 THE SPECIFIC INFLAMMATIONS (GRANULOMATA) 

MYCETOMA 

Mycetoma or Madura foot is a chronic specific inflamma- 
tory condition caused by the Actinomyces madurce. This 
organism closely resembles the A. bovis, but the club-shaped 
extremities are absent and spores may occur along the threads. 
Can be grown artificially; stains by the ordinary methods and 
by Gram's. 

Usually attacks but one foot, particularly the great toe, but 
may involve the leg, arm, or hand. A nodule slowly appears, 




Fig. S3- — Actinomyces of Madura Foot (Wright and Brown). 

Granule crushed beneath a cover-glass, showing radial striations in the 

hyaline masses. Preparation not stained; low magnifying power. 



and in the course of a year or two may soften and discharge 
a thin pus in which are found minute rounded bodies resem- 
bling fish-roe. These bodies may be either pinkish in color, 
the pale or ochroid variety, or black like gunpowder, the melan- 
oid form. 

On account of the degeneration numerous sinuses may form. 
The disease is painless and seldom fatal. 



PRIMARY LESION IO7 

SYPHILIS 

Is a specific, infectious, and very contagious disease of man. 
By experimental inoculation it has been transmitted to the 
higher apes and rabbits. 

Is due to the Treponema pallidum (Spirochceta pallida) , 
an organism that has been so constantly found in syphilitic 
lesions that it seems most probable that it is the causative factor. 
This organism is long, actively motile, spiral or corkscrew in 
shape, and with pointed ends. It is from 4 to 20 u long, 0.25 u 
thick, and contains six to fourteen turns which are short, clear 
cut and regular. It is difficult to stain and to grow, but it has 
been obtained in pure culture. 

The disease may be divided into the — 

1. Period of primary incubation, about three weeks. 

2. Period of primary symptoms, chancre and adenitis. 

3. Period of secondary incubation, about six weeks. 

4. Period of secondary symptoms, from one to three years. 

5. Intermediate period of two to four years, during which 
the patient may recover. 

6. Period of tertiary symptoms, unlimited. 

The primary lesion is the chancre, which starts as a single 
papule, seldom multiple, at the seat of inoculation, which may 
be either genital or extragenital, and is invariably present except 
in congenital syphilis. This soon becomes eroded as a result of 
superficial necrosis, but increases in size due to infiltration of the 
deeper tissues. Is circular or oval, 1 by 1.5 cm., base hard. The 
edges are sharply defined, the induration not extending much 
beyond the lesion, and terminating abruptly. The chancre is 
slightly elevated and movable, not being adherent to the under- 
lying tissues. Secretion is thin and scanty, suppuration being 
unusual; the surface may be dry or covered by a slight false 
membrane. 

Microscopically there is a tremendous infiltration of cells, 
particularly in the neighborhood of the vessels, and marked 
changes in the walls of the blood-vessels. The infiltration begins 
with an escape of small round lymphoid cells, and this is accom- 
panied by a proliferation of the cells of the cutaneous connective 
tissue and the cells of the walls of the blood-vessels. The elastic 



108 THE SPECIFIC INFLAMMATIONS (GRANULOMATA) 

tissue disappears, the new formation of cells extending along the 
small arteries and veins. The tissue becomes crowded with vari- 



■~i ■Pro':- 

O 0.'.' 



of 



6 o 






'<£> O '^'.(.•^ 







Fig. 34. — Section from a Primary Syphilitic Nodule of the Mucous 
Membrane of the Mouth, Showing Collections of Cells About 
the Blood-vessels in the Submucous Tissue (Delafield and 
Prudden) . 

ous kinds of cells — polymorphonuclear leukocytes, lymphocytes, 
plasma cells, endothelial and connective-tissue cells, and fibro- 
blasts. The media of the vessels thickens, the endothelium of 



TERTIARY LESION IO9 

the intima proliferates, and the lumen may be partially or com- 
pletely obstructed. As a result of the interference with the cir- 
culation degeneration begins. The vessels not infrequently 
show hyaline changes. 

Secondary Lesions. — From the time the chancre begins to 
form the spread of the disease begins by invasion of the lymph- 
atics. By the time the chancre is well developed enlargement of 
the neighboring lymph-nodes can be observed. This continues 
even after the chancre has disappeared, and the enlarged nodes 
are found to be hard, free from inflammation, painless, and 
movable. They also do not suppurate. The nodes most com^ 
monly involved are the postcervical, sternomastoid, submaxil- 
lary, epitrochlear, axillary, and inguinal. Enlargement of the 
epitrochlear is particularly suspicious, as it is seldom attacked 
except in syphilis. 




Fig. 35. — Upper Median Incisors Fig. 36. — Serrations in Normal 
in Hereditary Syphilis (Cor- Teeth (Cornil and Ranvier). 

nil and Ranvier). 

There then appear skin eruptions, polymorphic in character, 
accompanied by fever, constitutional symptoms, and a rapid 
decrease in the erythrocytes, with a moderate leukocytosis, 
usually of the lymphocytes. The skin lesions are generally 
symmetric, do not itch, and are coppery in appearance. May be 
some loss of hair, due to inflammation of the hair-follicles. The 
patches are irregular and have a "moth-eaten" appearance. 

The mucous patch or condyloma latum appears on the mucous 
membrane and the contiguous skin surfaces, particularly those 
that are naturally warm and moist. It is a slightly elevated, 
moist, grayish lesion, covered by a thin pseudomembrane. In 
these there is round-cell infiltration of the skin, with superficial 
necrosis and edema. There may be one or more patches. 

Although the chancre and the secondary lesions are highly 
contagious, the mucous patch is probably the most so. 

The chief tertiary lesion is the gumma. It is found most 
commonly in the nose and nasal septum, scalp, iris, shoulders, 



IIO THE SPECIFIC INFLAMMATIONS (GRANULOMATA) 

arms, and internal organs. The gumma develops as a nodular 
mass composed of great numbers of embryonic connective tissue 
and lymphoid cells with a very small amount of trabecular 
Blood-vessels, most of them showing thickening of their walls, are 
numerous and may be found even during necrotic changes of 
the tissues. This would indicate that the breaking down proc- 
esses are probably due largely to the syphilitic poison and not to 
obstruction of the vessels. It usually undergoes a caseous or 
other form of degeneration, with ulceration or absorption and 
subsequent cicatrization. It is hard, dense, and elastic. 

When the growth of the gumma ceases, the younger per- 
ipheral cells become organized into connective-tissue cells, 
forming an envelope for the cheesy and gummatous center. 
This envelope shrinks, the semifluid portions are absorbed, 
and finally a scar, possibly calcareous, is left. 

The blood-vessels show an endarteritis which closes or 
narrows the lumen. The remains of broken-down cells and 
particles of fat are present, and giant cells may be found. As 
the Treponema pallida have been found in gummata, and inocu- 
lations into apes have caused syphilis, the tertiary lesions must 
be considered infectious. 

Congenital syphilis may result from disease of the ovum, 
spermatozoon, or both, or it may be transmitted through the 
placenta after conception has taken place, this being the most 
probable. 

The mother, although showing no signs of syphilis, cannot 
be infected by nursing, her child that is suffering from the 
disease (Colles' law). 

Whether this immunity is real or whether the mother ac- 
quires it by being herself affected, although so lightly as to 
cause none of the usual symptoms, is still an unsettled question. 
As the Wassermann reaction is generally positive with the 
mother's serum, it would seem that she is usually infected. 

An apparently healthy baby born of a syphilitic mother 
cannot be infected by her (Prof eta's law). This apparent im- 
munity may indicate that the child has received a true but 
latent infection, one that may not make its appearance until 
later in life. 



CONGENITAL SYPHILIS III 

The fetus may die in utero and be aborted, the child may 
be born dead, or it may be alive, but die shortly after birth. 

The primary lesion does not occur in the hereditary form, 
but the secondary and tertiary manifestations may be evi- 
dent, such as skin eruptions and mucous patches or even gum- 
mata. The characteristic lesion of congenital syphilis is pemphi- 
gus. There are present on the palms or the soles blister-like 
elevations of the skin containing a bloody or a greenish fluid. 

The upper incisors of the second dentition are frequently 
conical and peg shaped, with deep notches at the free edge 
(Hutchinson's teeth). 

There also frequently occurs a "white" pneumonia, cir- 
rhosis of the liver, spleen, and pancreas, osteochondritis, and 
interstitial keratitis. 



CHAPTER VIII 
PROGRESSIVE TISSUE CHANGES 

HYPERTROPHY 

Hypertrophy, generally speaking, means an enlargement 
or overgrowth of any kind. It is usually divided into true and 
false hypertrophy, or hyperplasia, as the latter is called. 

True hypertrophy is a uniform enlargement of a part, de- 
pendent upon an increase in size of all of its component elements. 
Accompanying the enlargement there is an increase in the 
functional power of the part involved. 

The hypertrophy may be either congenital or acquired. It 
may also be either physiologic or pathologic. The former, 
however, may come under the latter heading when it reaches 
a degree that is not normal to the individual. 

Hypertrophy is called compensatory when one organ takes 
upon itself the amount of work that was primarily carried on 
by two; is known as vicarious when another function increases 
at the expense of one that has been destroyed. 

Etiology. — i. Congenital causes, in which case there are marked 
overgrowths of portions of the body, especially of the fingers 
and toes. 

2. Exercise calls for an increased amount of energy. This 
demand is met by a greater supply of food with a subsequent 
increase in size, and is seen in the enlarged muscles of a black- 
smith, or in a kidney when the other one is diseased or absent. 
This latter is an example of compensatory hypertrophy. 

3. Nervous influences in some indefinite way play a part in 
hypertrophy, as is seen in the enlargement and increased func- 
tion of the mammary glands during pregnancy. 

4. Disease of the hypophysis cerebri apparently causes the 
condition called acromegaly, in which the tissues of the face 
and extremities hypertrophy. 



HYPERPLASIA, OR FALSE HYPERTROPHY 113 

Morbid Anatomy. — The part affected is uniformly increased 
in size. 

Microscopically hypertrophy may be divided into the simple 
or true and the numeric (hyperplasia) . 

In the simple there is an increase in the size of the individual 
cell. This is seen particularly in the pregnant uterus, where 
at term the unstriped muscle cells may be eleven times as long 
and four times as broad as normal. 

In the numeric variety the cells increase in number, but not 
necessarily in size; may even be smaller than normal. 

Hyperplasia, or false hypertrophy, is a condition in which 
there is an increase in number of the cells with usually an 
asymmetric enlargement of the tissue. It is an excess of one 
constituent of an organ without a corresponding growth of the 
other elements. 

The fibrous connective tissue is most commonly involved. 

Etiology. — 1. Irritation is the most common cause, if not 
too severe in character. In that case inflammation with con- 
sequent degeneration results. 

The irritation may be mechanical, such as results from in- 
termittent pressure exerted by tight shoes, or from the presence 
of a foreign body. Chemical irritants, such as alcohol, will 
bring about an increase in the amount of connective tissue, par- 
ticularly in the liver, in which case there is also an increase 
in the number of bile capillaries. 

2. Nervous influences, such as bring about the condition 
known as pseudohypertrophic muscular paralysis. In it there 
is not an increase in the muscle itself, but the fat has under- 
gone a hyperplasia. There is also a fatty degeneration, with 
atrophy of muscle-fibers. 

3. Compensatory, such as occurs when, on account of the 
decrease in size of an organ, the surrounding tissues have 
undergone a hyperplasia in order to supply the deficiency. 

Morbid Anatomy. — The part involved may be much larger 
than normal or, on account of the contraction of the newly 
formed connective tissue, be much smaller. In either case 
the change is not symmetric. 

In elephantiasis the part involved will be irregularly enlarged 



114 PROGRESSIVE TISSUE CHANGES 

as a result of the obstruction of the lymphatics and the increase 
in the number of cells. 

In hyperplasia of the connective tissue of the liver the organ 
may be smaller than normal and have a roughly granular surface. 

Metaplasia refers to the transformation of one tissue into 
one of another variety. The new variety must, however, be 
one derived from the same blastodermic layer. There is not, 
however, a development of less specialized tissues into a higher 
type; a simple epithelium cannot, in the vertebrates, give rise 
to a more complex glandular tissue or to nerve-cells. Colum- 
nar epithelium may become converted into stratified squamous 
epithelium with keratosis, as in the uterus, gall-bladder, or 
larynx. This change is more common in the connective-tissue 
group, as in the formation of fat from areolar tissue, of bone 
from fibrous tissue, etc. 

Heteroplasia is the development of a new tissue in a locality 
where it is not normally found. This is seen particularly in 
connection with neoplasms. 

Anaplasia refers to the reversion of a cell to a less specialized 
stage. It is a change occurring preparatory to an increased 
proliferation. Is applied mainly to tumor formation. Hanse- 
mann's studies of tumor cells show that unequal, asymmetric 
and multipolar mitosis, and destruction of chromosomes is of 
frequent occurrence, especially in the more malignant tumors. 
The term "anaplasia" is applied to these cells, signifying a loss 
of normal differentiation, of specific function, and of organ- 
ization. 

Anaplastic cells are, therefore, not embryonal cells, but a new 
type which has lost its place in the old organization. 



CHAPTER DC 



TUMORS OR NEOPLASMS 



A tumor is an abnormal mass of cells or tissues resembling 
those normally present, but arranged atypically. It grows 
without any definite limit at the expense of the organism, with- 
out serving any useful function. 

The cause of such growths is as yet unknown. They are 
made up of tissues that have their counterpart either in the 
embryonal or adult development. They differ in having a 
more or less atypical arrangement, in occurring in tissues 
in w T hich they are heterologous, and in not having any mechan- 
ism to control their growth and function. Inflammation is 
unessential to their occurrence, and their structure is dissimilar 
to that of inflammatory lesions. There is no hyperemia, no 
exudation, no leukocytic invasion, no granulation tissue, no 
cicatrization. Tumors tend to increase and persist, while most 
inflammations tend to recover and disappear. Inflammatory 
growths always consist of connective tissue, regardless of the 
tissue or organ in which they occur. 

Theories of Origin. — They are numerous, but as yet no one 
answers in every case. 

i. Spermatic Influence. — It was thought that the normal 
tissue where the growth occurred had become directly trans- 
formed into the tissue of the tumor, but this is not in any way 
supported. 

2. Mechanical Irritation Theory of Virchow. — By this it is 
claimed that new growths arise in tissues that have been the 
seat of injury or chronic irritation. Such cases as the develop- 
ment of epithelioma ta on the lower lips of pipe-smokers, car- 
cinoma of the gall-bladder associated with gall-stones, scrotal 
cancer in chimney-sweeps, rr-ray cancer, cancer of mouth in 
Ceylon, Kangri cancer in natives of Kashmir, etc., would seem 

115 



Il6 TUMORS OR NEOPLASMS 

to uphold this theory. It is probable, however, that the in- 
juries and irritation are not the causative, but are predispos- 
ing, factors. 

3. Theory of Embryonic Remnants (Cohnheim). — The author 
of this theory believed that "in an early stage of embryonic 
development more cells were produced than were required for 
the formation of the tissue involved, so that there remained un- 
used a number of cells, possibly very few, which, on account 
of their embryonic character, were endowed with the power 
of marked proliferation." These remnants are frequently 
spoken of as "rests." Cohnheim thought that they could lie 
latent for many years and develop in after-life if conditions 
should become favorable. No explanation is given, however, 
as to what is meant by "favorable conditions." 

Such groups of cells have been observed not infrequently 
in various tissues and organs of the body. Adrenal rests 
are not uncommon. In certain forms of tumors this theory 
seems to hold good: in enchondromata of the testis and parotid 
glands and of other organs, and particularly in the case of the 
dermoid cysts. 

4. Parasitic or Infective Theory. — It has been claimed by many 
investigators, especially concerning the carcinomata and sarco- 
mata, that tumors are caused by the presence of living micro- 
organisms. Bacteria were first supposed to be the cause, but 
protozoa and blastomycetes have also been suspected. The 
general opinion, however, is that these cell inclusions are por- 
tions of broken-down nuclei or else secretions of the cells. At- 
tempts to grow these bodies have, as a rule, resulted in failures, 
or, if grown, have not reproduced the disease in other animals. 
Up to the present no specific micro-organism has been demon- 
strated in cancer or in any other spontaneous new growth. 
Attempts to transplant human carcinoma from one person to 
another have not as yet been successful, although transplants 
of tumors have been made in many generations of mice and 
rats. Success occurs only when the growth has been implanted 
in other animals of similar kind. Such experiments, neverthe- 
less, do not show the necessity of any low form of organism. It 
is well known that portions of skin can be transplanted from 



THEORIES OF ORIGIN 117 

one person to another. More recently attempts have been 
successful in causing sarcoma-like tumors to grow in hens 
that have been inoculated with a filtered extract of the 
growth. 

5. Theory of Decreased Tissue Resistance. — Ribbert's theory 
is that the connective tissue loses its normal resisting power or 
" tissue tension," and by doing so allows the epithelial cells 
to undergo abnormal proliferation. The essential feature is 
that the cells must become separated from their normal re- 
lation to the surrounding tissue and then take on an active 
growth. 

This theory is not satisfactory, as in the healing of wounds 
scattered groups of epithelial cells are found constantly which 
have actively pushed over and into the underlying granulation 
tissue, yet tumor formation in such cases is exceptional. 

6. Nervous Theory. — This was to the effect that through 
disturbances of the trophic nerves the tissues were able to un- 
dergo an overgrowth. Certain investigators have shown what 
seems to be a definite correspondence between the occurrence 
of skin cancer and the distribution of certain cutaneous 
nerves. 

Of other theories, that of Adami is interesting. According to 
him the cell, instead of adhering to the habit of function, has 
reverted to an earlier stage, one in which the habit of growth 
predominates. The energy, therefore, that primarily was 
devoted to the performance of function is now directed to 
growth, and there is then formed a mass of uncontrolled 
cells. This view gains support in that many of the malignant 
tumors appear at a time when the function of the tissue is at a 
decline. 

A general survey of the field would indicate that true tumors 
are not parasitic in nature. That the condition is one in which 
the potential activity of the cell is sufficient to give rise to un- 
limited growth if the restricting barrier, whatever that may be, 
be removed. To that extent the cancer cell itself may be con- 
sidered in the light of a parasite. It has been shown that in the 
rat certain tissues ordinarily resistant to the implantation of 
bits of rat tumor may become susceptible as a result of some 



Il8 TUMORS OR NEOPLASMS 

pre-existing irritation, To this condition has been applied the 
term precancerous stage. In the human being there are certain 
lesions of the mammary gland that although in themselves 
non-cancerous may later become so. 

Predisposing Causes. — Age. — Certain tumors apparently 
bear a distinct relationship to the age of the individual. Before 
thirty years the sarcomata are most likely to appear; after that 
period, the carcinomata. 

Sex. — On account of the frequent involvement of the female 
genitalia women are much more commonly the victims of cancer 
than men. 

Heredity may have some influence, as it has been found 
that carcinomata are more common in some families than in 
others. 

Occupation, as in chimney-sweepers and in paraffin- workers, 
who seem to frequently suffer from carcinoma. Probably the 
result of chronic irritation due to a lack of cleanliness. 

Morphology. — Tumors may differ greatly in the follow- 
ing respects: 

Size. — They may be of any size, from microscopic to weighing 
275 pounds, as reported by Delameter. 

Shape. — According to their shape tumors are called nodu- 
lar when spheric, tubercles when projecting as a rounded 
body above the surface of an organ, flat or tabular when rising 
as a comparatively level elevation. 

When the growth is connected to its original site by a stalk 
or pedicle it is called a polyp. When the surface is very rough- 
ened and irregular the tumor may be termed a cauliflower or 
dendritic growth. 

If like a mushroom with a narrow stalk and a broad head, 
it is termed a fungus. 

Color. — The color of a growth depends upon the nature of 
the tissue of which it is composed, upon the amount of blood 
present, and the presence of pigment. It may also be modified 
if degenerative processes have taken place. 

Consistency depends upon the structure of the growth and 
upon the presence or absence of degenerations. If of bone the 
tumor will be very hard; if of mucous tissue, very soft. 



MORPHOLOGY 119 

Number. — Tumors may be single or multiple, there being 
usually a single primary tumor with several secondary ones if 
the growth is malignant, these latter being of the same type 
as the primary. There may, however, be hundreds of primary 
tumors, as in cases of fibroma molluscum. Sometimes there may 
be several primary tumors of different histologic types. 

A recurrent tumor is one that recurs at the place from which 
it was removed. 

According to the arrangement, tumors may be typical, hemo- 
plastic, or homologous when they resemble the tissue from which 
they arise; atypical, heteroplastic, or heterologous when they 
differ. 

If made up of a simple tissue they are called histoid tumors; 
if of a combination, attempting the formation of an organ, 
organoid; and when containing portions of all three blastodermic 
layers, teratoid. 

The blood-vessels, which always originate from pre-exist- 
ing vessels, may be greatly increased in number, telangiec- 
tatic; in size, cavernous; or unusually arranged, plexiform. 
These may be greatly decreased in number, thereby favor- 
ing secondary changes, or their walls may be imperfectly 
formed, giving rise to hemorrhages. Capillaries are commonly 
absent. Lymphatics are usually present, but the nervous sup- 
ply is very poor, as a rule. 

The growth of a tumor is independent of that of the indi- 
vidual. It may continue even if the normal tissues are being 
sacrificed for it. A lipoma will grow although the patient 
may not be getting sufficient nourishment to carry on the 
normal functions of the body. 

It may be either central expansion, as is the case in benign 
growths, or peripheral infiltration, as in the malignant forms. 
The latter also increase by means of the central expansion. 

As the blood-supply of tumors is usually poor, they fre- 
quently undergo various forms of degeneration, as pigmentation, 
calcification, fatty, hyaline, colloid, and mucoid metamorphoses; 
necrosis and ulceration. 

According to their effect upon the individual a new growth 
may be either benign or malignant. 



120 TUMORS OR NEOPLASMS 

Benign growths do not affect the patient except as they 
may press upon vital structures or undergo degenerative proc- 
esses. 

They are usually circumscribed, encapsulated, do not give 
metastases, and do not recur after excision. 

Malignant tumors are those that through their own influences 
tend to bring about the death of the individual. They are not 
circumscribed nor encapsulated, cause cachexia, probably toxic 
in origin, give metastasis, and recur after excision. 

Metastasis refers to the extension of the primary growth 
by the transference of malignant cells to other parts of the 
body. In carcinoma this takes place, as a rule, by means of the 
lymphatics. As the original tumor increases in size its cells 
penetrate the surrounding tissues, and on account of the de- 
creased resistance tend to grow along the lymphatic spaces. 
In this way distant growths may be directly connected with the 
primary focus by means of these strands. This is frequently 
spoken of as the permeation method. As the tumor extends, it is 
the neighboring lymph-nodes that first show secondary involve- 
ment. The extension continues until a chain of lymph-nodes is 
attacked. It is also very probable that extension by means of 
the blood may occur indirectly in carcinoma. The tumor cells 
may gain entrance to the thoracic duct and thus get into the 
circulation. They then usually lodge in the liver and give rise 
to new masses. Under other conditions, such as necrosis 
and ulceration, the cancer cells can enter directly into the 
blood. 

In sarcoma extension takes place only by means of the blood, 
the walls of the vessels being very incomplete and easily allow- 
ing the entrance of tumor cells. 

Death may be caused by tumors — 

i. Pressing upon vital organs. 

2. Invading vital organs and causing degeneration. 

3. Hemorrhage resulting from ulceration and degeneration. 

4. Absorption of poisonous products. 

5. Secondary infection. 

6. Exhaustion due to the tumor using up so much nutrition 
for its own benefit. 



CLASSIFICATION OF TUMORS 121 

Classification of Tumors. — The simplest is as follows: 
I. Histoid. 

Simple Connective-tissue Tumors. 

Atypical. Typical. 

Embryonic type Sarcoma. Connective tissue. 

Adult type Fibroma < ^ r. > Connective tissue. 

Lipoma. Fatty tissue. 

Myxoma. Mucous tissue. 

Chondroma. Cartilage. 

Osteoma. Bone. 

Glioma. Neuroglia. 



Myoma -J 



Specialized Connective-tissue Tumors. 

Rhabdo- Striated muscle. 

Leio- Non-striated muscle. 

Hemangioma Blood-vessels. 

Lymphangioma Lymph- vessels. 

Lymphadenoma Lymphatic tissue. 

Lymphoma Lymphatic tissue. 

Type of Endothelium. 
Endothelioma. 

II. Ok ganoid. — Epithelial Tumors. 

Neuroma Nerve tissue. 

Squamous epithelioma Squamous epithelium. 

Hard papilloma Squamous epithelium. 

Soft papilloma Columnar epithelium. 

Cylindric epithelioma Columnar epithelium. 

H^Zephroma } Nomal « landukr ^ of « Us - 

Carcinoma Atypical glandular cells. 

III. Teratoid. — Mixed Tumors. 

Dermoids. 
Teratoma. 
Cholesteatoma. 

IV. Chorio-epithelioma, Syncytioma Malignum. — De- 
ciduoma Malignum. 

Combinations of tumors that have been derived from the 
same blastodermic layer frequently occur, as fibrosarcoma, 



122 TUMORS OR NEOPLASMS 

fibromyoma, etc. One type, however, cannot be transformed 
into another. 

The following classification of Adami's is recommended as 
being the most logical on account of its having been based 
upon a careful study of the histogenesis of the tissues. 

Adami explains the classification as follows: "We thus find 
that the embryo comes to exhibit cell collections of two orders, 
which may be termed 'lining membranes' and (for lack of a 
more expressive word) 'pulps,' the 'lining membranes' being the 
persistent epiblastic, hypoblastic, mesothelial, and endothelial 
layers, the 'pulps' being the main mass of the neuroblast (of 
epiblastic origin) , the notochord (of hypoblastic) , and the mesen- 
chyme (of mesoblastic) . And now, following up the develop- 
ment of these different cell collections, we observe that the 
adult tissues derived from these two series exhibit well-marked 
differences, so that we can divide adult tissues into two great 
groups — the lepidic (from tents, Asiudo?, a rind, skin, or mem- 
brane) and the hylic (oXtj, crude undifferentiated material). 

"The characteristic of the lepidic tissues is that the spe- 
cific cells which give them their main features are arranged 
either in layers or clusters in direct apposition; they are not 
separated by lymph-spaces or by blood-vessels ; they possess, never- 
theless, a supporting framework or stroma of hylic tissue in which 
run the nutrient vessels. Of the hylic tissues, the features are 
the opposite : separating the cells there is a matrix of intracellular 
substance, either homogeneous or fibrillated, while lymph-spaces 
and blood capillaries tend to separate and run between the indi- 
vidual cells. 

"If in the lepidic tissues there is a stroma of hylic tissues, so 
here in the hylic there always enters lepidic tissue in the shape 
of the living endothelium of the blood- and lymph- vessels. In 
either case the elements of the other order occupy a subordinate 
position. While some pathologists, like O. Israel and Buxton, 
have already noticed this distinction, the histologists and embry- 
ologists have laid little stress upon it. The more we study 
tumors, the more we realize the importance of the distinction." 

On this basis we obtain the following classification of normal 
tissues : 



CLASSIFICATION OF TUMORS 1 23 

I. LEPIDIC, OR LINING MEMBRANE TISSUES, 

in which tlie blood-vessels do not penetrate the groups of specific cells and in 
which there is an absence of definite stroma between the individual cells, although 
such stroma, of mesenchymatous origin, may be present between the groups 
of cells. 

1. Epiblastic: 

Epidermis. Epidermal appendages of the hair, nails, enamel of 
the teeth, etc. Epidermal glands. Epithelium of the mouth and 
salivary glands. Epithelium and glands of the nasal tract and 
associated spaces. Epidermal portion of the hypophysis cerebri. 
The lens of the eye. Epithelium of the membranous labyrinth 
of the ear, anus, and male urethra (except the prostatic portion). 

2. Hypoblastic: 

Epithelium of the digestive tract and glands connected with it. 
Specific cells of the liver, pancreas, tonsils, thymus, and thyroid. 
Epithelium of the trachea, lungs, bladder, female urethra, and 
male urethra (prostatic portion). 

3. Mesothelial: 

Lining cells of the pleurae, pericardium, peritoneum. Specific cells 
of the suprarenals, kidneys, testes, and ovaries (Graafian follicles). 
Epithelium and glands of the Fallopian tubes, uterus, vagina, 
vasa deferentia, vesiculae seminales, etc. 

4. Endothelial: 

Lining endothelium of the blood-vessels and lymphatics. 

II. HYLIC, OR PRIMITIVE PULP TISSUES. 

Organs and tissues in which the special characteristic is that the specific 
cells lie in, and are separated by, a definite stroma, homogeneous or fibrillar, 
in which there may or may not be blood and lymph-vessels. 

1. Epiblastic: 

Nerve-cells; neuroglia. 

2. Hypoblastic: 

Notochord. 

3. Mesenchymatous: 

Fibrous connective tissues, cartilage, bone, reticulum of lymph- 
glands, bone-marrow, fat-cells, involuntary muscle tissue, spleen, 
blood-vessels, blood-corpuscles. 

4. Mesothelial: 

Striated muscle, including cardiac muscle. 

"Following this scheme of classification of the normal tissues, 
we may now divide the tumors arising from the specific constitu- 
ent cells of the various tissues into two main genera — the lepidic 
tumors or lepidomata, originating from the above lining mem- 
brane' tissues and the hylic tumors (hylomata), originating from 
tissues derived from the embryonic 'pulp.' We can further 
distinguish two broad groups of lepidic tumors — the primary, 
those whose cells are derived in direct descent from the original 
epiblast and hypoblast, and the secondary, or transitional, whose 



124 TUMORS OR NEOPLASMS 

cells are derived in indirect descent from the same — i. e., have 
in the course of development passed through a mesoblastic or 
mesenchymatous stage before coming to form portions of a 
lining membrane." 

In the classification that follows the author has not fol- 
lowed the exact wording of Dr. Adami, but has introduced such 
modifications as shall be consistent with his own text: 

I. LEPIDIC, OR RIND TUMORS. 

A. Lepidomata of the First Order. 
i. Of Epiblastic Origin. 

Tumors (epitheliomata) whose characteristic constituents are over- 
growths of tissues derived directly from the epiblastic "lining 
membranes" or epiderm. 
(a) Typical. — Papilloma. 

Adenoma of the sweat-glands. 
Adenoma of the sebaceous glands. 
Adenoma of the mammary glands, etc. 
(b) Atypical. — Squamous-cell carcinoma. 

Carcinoma of glands of epiblastic origin. 

2. Of Hypoblastic Origin. 

(a) Typical. — Papilloma of the digestive and respiratory organs and 
bladder. 
Adenoma of the digestive and respiratory tracts, thy- 
roid, pancreas, liver, bladder, etc. 

(b) Atypical. — Carcinoma developing in the same organs and regions. 

B. Lepidomata of the Second Order or Transitional Lepidomata. 

3. Of Mesothelial Origin. 

Tumors (mesotheliomata) whose characteristic constituents are cells 
derived in direct descent from the persistent mesothelium of the 
embryo. 

(a) Typical. — Adenoma of the kidney, testicle, ovary, urogenital 

ducts; uterus, prostate. 
Mesothelioma — adenoma of the serous membranes of the 
pleura, peritoneum, etc. 

(b) Atypical. — Cancer of the above-mentioned organs; squamous 

endothelioma, so-called, of serous surfaces, epithe- 
lioma of the vagina; adrenal mesotheliomata, hyper- . 
nephroma. 

4. Of Endothelial Origin. 

Tumors (endotheliomata) originating from the endothelium of the 
blood- and lymph- vessels: 

Lymphangio-endothelioma. 

Hemangio-endothelioma. 

Perithelioma. 

Cylindroma. 

Psammoma. 

Cholesteatoma. 



SARCOMA 125 

II. HYLIC, OR "PULP" TUMORS. 

1. Of Epiblastic Origin. 

Tumors whose characteristic constituents are overgrowths of tissues 
derived from the embryonic pulp of epiblastic origin. 
(a) Typical. — Neuroma. 

Glioma. 
(b) Atypical. — Gliosarcoma. 

2. Of Hypoblastic Origin. 

Tumors derived similarly from embryonic pulp of hypoblastic origin. 
Chordoma. 

3. Of Mesenchymal Origin. 

A. Mesenchymal Hylomata. — Derived from tissues originating from 

the persistent mesoblastic pulp or mesenchyme, 
(a) Typical. — Fibroma. 
Lipoma. 
Chondroma. 
Osteoma. 
Myxoma. 
Leiomyoma. 
Angioma. 
Myeloma. 
Lymphoma. 
(b) Atypical. — Derived from mesenchymatous tissues. 
Sarcoma. — Fibrosarcoma. 

Spindle-cell sarcoma. 

Oat-cell-shaped sarcoma. 

Chondrosarcoma. 

Osteosarcoma. 

Myxosarcoma. 

Lymphosarcoma . 

Chloroma. 

Angiosarcoma. 

Melanosarcoma (debatable). 

B. Mesothelial Hylomata. — Tumors which are overgrowths similarly 

of tissues derived from embryonal pulp of definitely meso- 
thelial origin. 
Rhabdomyoma. 

TUMORS OF EMBRYONAL CONNECTIVE TISSUE 

SARCOMA 

A sarcoma is a tumor made up of cells that resemble physically 
those found in embryonal connective tissues. As a rule the 
greater the departure from the adult cell, the greater is the 
malignancy. They are characterized by the preponderance of 
the cells over the intercellular substance, which may be granular, 
fibrillary, or reticular. The sarcoma cells are not truly embryo- 
nal, as they never continue to a complete development. They 



126 TUMORS OR NEOPLASMS 

arise from the mesoblastic layer and often retain the char- 
acteristics of the tissue from which they arise, periosteal sar- 
comata sometimes containing bone. 

The sarcomata are essentially malignant; that is, they in- 
filtrate the surrounding tissues, give metastases, cause cachexia, 
and return after excision. It is only occasionally that they are 
encapsulated. 

The blood-vessels are generally few in number and imper- 
fectly formed, the single layer of endothelium being supported 
by a very few connective-tissue fibers. In many cases the 
blood-channels are simply spaces whose walls are formed by the 
tumor cells. The imperfect vessel wall explains why hemor- 
rhage in these tumors is so common and why metastasis takes 
place by means of the blood. 

Sometimes the blood-spaces may be very large and numer- 
ous, thus forming the angiosarcoma. 

As a rule, no lymphatics are present. 

Sarcomata may occur in any part of the body; as a rule, they 
are seldom primary within organs. 

They generally occur before the age of thirty. Are fre- 
quently rounded in shape, somewhat lobulated, and to a cer- 
tain degree circumscribed. Are hard or soft according to the 
amount of intercellular substance present, or to the variety of 
the tissue of which they are composed. 

Their color is generally pink or grayish; this, however, de- 
pends to a great extent upon the condition and number of the 
blood-vessels. 

On account of the poor blood-supply, degenerations, par- 
ticularly myxomatous, frequently take place. Interstitial hem- 
orrhages as a result of the degeneration are not infrequent. 

If there is pigment present, either melanin or hemosiderin, 
the tumor is called a pigmented one. 

These tumors vary greatly in their malignancy, the small 
round-cell type, especially if melanotic, being rapidly fatal. 
The greater the amount of cellular elements, the greater is 
the malignancy. 

The varieties of the tumors depend upon the kind of cell 
that predominates. 



VARIETIES OF TUMORS 



r 




i 







127 



Fig. 37. — Small Round-cell Sarcoma of the Lower Jaw. Oc. 3; ob. 
D. D. (McFarland). 



its 



'it" 



a TO* 





















i33 a^ ---« m - rc\ ^^ <= 



~3s 



^^* ^ * * 



*^ 



^N^^bSS 









^■tv 3 









vs 






v^ 






Fig. 38. — Spixdle-cell Sarcoma from the Brain. X 300 (Diirck). 
1, Spindle cells cut longitudinally; 2, spindle cells in transverse section. 



128 



TUMORS OR NEOPLASMS 



Round-cell sarcomata are those made up of either large or 
small round cells. 

In the small-cell variety the intercellular substance is very 
scanty. They are rather soft, whitish in color, friable, and 
a milky juice can be scraped from the cut surface. 

They grow rapidly, infiltrate the surrounding tissues, give 
extensive metastasis, recur quickly after removal, and soon 




Fig. 39. — Giant-cell Sarcoma of the Thigh (McFarland). 
a, Giant cells; b, spindle cells. 



cause death. They may occur in any part of the body and at 
any age. 

The individual cells have large vesicular nuclei, that stain 
deeply, and comparatively little protoplasm. 

If there is a close resemblance to the arrangement of a lymph- 
node, small round cells with a distinct reticulum, the tumor 
is called a lymphosarcoma. 



VARIETIES OF TUMORS 120, 

The large round-cell sarcoma is very similar to the small, 
but is firmer on account of the intercellular connective tissue 
present. The cells are larger, and although generally round, 
may be polygonal, and are sometimes arranged in alveoli. 

Are less malignant than the small. 

Spindle-cell sarcoma is one that is made up of spindle cells, 
either large or small. Is one of the commonest forms. 







« * © * ® £ ■■■© ©#? @> - » a • * ^ o ■ ?\g> ®g> y 

Fig. 40. — Alveolar Large Round-celled Sarcoma irom the Perios- 
teum. X 250 (Diirck). 
1, Heavy septum of connective tissue; 2, delicate connective-tissue reticu- 
lum; 3, polyhedral cells with vesicular nuclei. 

These tumors are quite firm, white, and very little juice can 
be scraped from the cut surface. The cells are arranged in 
irregular bundles and have oval vesicular nuclei. The amount 
of intercellular tissue may be very great, making the tumor 
quite hard; is then known as a, fibrosarcoma and is but slightly 
malignant. It is often difficult to determine whether the tumor 
is a sarcoma or a fibroma. 



130 



TUMORS OR NEOPLASMS 



The spindle-cell sarcomata are relatively benign; they fre- 
quently do not give metastasis, although recurring after removal. 

Giant-cell sarcoma is one in which there are found cells made 
up of a large amount of cytoplasm in which are numerous oval 
nuclei centrally located. The predominating cells may be round 
or spindle shaped. They are most commonly found in relation 
with bone and periosteum. When occurring on the jaw are 




Fig. 41. — Alveolar Small Round-cell Sarcoma. 

(McFarland). 



sometimes referred to as epulis, although the same term may be 
applied to a simple fibrous tumor. 

This form is the least malignant of all the sarcomata. 

Special names have been given to other forms of sarcoma 
on account of some special feature. 

Alveolar sarcoma is where either groups of round or spindle 
cells are surrounded by distinct bands of connective tissue. This 
form may very closely resemble carcinoma. 



VARIETIES OF TUMORS 13 1 

Melanotic sarcoma is one of any type in which there is melanin 
present. This pigment may be found either in the cells or in 
the intercellular tissue. 

They occur in the skin, the choroid coat of the eye, and in 
the ciliary body. 

Are very malignant, give widespread metastasis, and rapidly 
prove fatal. The liver is the common secondary seat, particu- 
larly after primary melanotic sarcoma of the eye. 



-% 



*Zsr% 







$ o 







Fig. 42. — Metastatic Melanosarcoma of the Peritoneum. X 320 

(Diirck). 
1, Nests of darkly pigmented polygonal cells; 2, cross-section of vessels. 

Myxosarcoma is one in which there is a marked mucoid 
degeneration present. 

Angiosarcoma is a growth that contains many blood-vessels. 
If the walls of these vessels or the neighboring cells undergo 
a hyaline degeneration, the sarcoma is spoken of as a cylin- 
droma. 

If the tissue with the exception of those cells in the imme- 
diate neighborhood of the vessels undergoes a mucoid change, 
the growth is called a my xangio sarcoma tubulare. 



132 



TUMORS OR NEOPLASMS 



Chloroma is a variety of sarcoma arising from the perios- 
teum of the skull; is greenish in color. It may be that this form 
is more closely related to the tumor formations occurring in 
leukemia. 

Psammoma is a tumor allied to the sarcoma. It is made 
up of masses of spindle cells, which contain areas of hyaline 



W* 




Fig. 43. — Perithelioma of the Retina (McFarland). 

a, Blood-vessels surrounded by cells in a good state of preservation; b, 

degenerated portion of tumor. 

degeneration and calcification. Are usually found in the 
meninges of the brain and spinal cord. 

Endothelioma is a tumor arising from endothelial cells. These 
growths are at times very difficult to differentiate from carcinoma 
on account of the apparent cell nest arrangement, but careful 
examination will commonly show some sarcomatous areas. 



VARIETIES OF TUMORS 



133 



The cells extend along the lymphatic spaces and are closely 
related to connective tissue. Are found in the serous mem- 
branes, testicle, ovary, liver, and parotid. Are malignant. 

Under this same heading are included those tumors developing 
from the cells in the lymph-spaces, the lymphangio-endothelioma; 
and those from the endothelium of the blood-vessels, the heman- 




Fig. 44. — Endothelioma of the Pleura. Zeiss, Oc. 2 ; ob. c. (McFarland). 
The illustration shows the cellular growth in the form of cylindric masses 
which fill crevices of the tissue, probably originally channels. 



gio-endothelioma. Occasionally some of these tumors arise from 
the perivascular endothelium, and to these has been given the 
name perithelioma. The cells in these latter are arranged in 
strands radiating from the vessel around which the mass orig- 
inated. 

According to the combination of tissues present sarcomata 



134 



TUMORS OR NEOPLASMS 



maybe further classified as follows; all such varieties, however, 
not being mentioned: 

Osteosarcoma = bone present. 

Chondrosarcoma = cartilage present. 

Myosarcoma = muscle present. 

Neurosarcoma = nerves present. 

TUMORS OF ADULT CONNECTIVE TISSUE 

Fibroma is a tumor of fibrous connective tissue. Fibro- 
mata are usually pale in color, round, lobulated, circumscribed, 
and encapsulated. They may be of varying degrees of firmness. 




Fig. 45-- 



-Fibroma. Cells and Fibrils in Small Bundles which Run 
in Every Direction (Mallory) . 



The cells resemble those of normal connective tissue and 
are arranged in bundles that cross each other in all directions. 

In the soft variety the cells are separated by serous or mucous 
deposits. 

In the hard variety the cells are closely packed together. 



LIPOMA 135 

Fibromata are benign and frequently undergo various de- 
generations. Occur in all parts of the body, particularly 
in the uterus, where they attain great size. In this locality 
are usually combined with muscle tissue, forming the fibro- 
myomata. 

They may occur in combination with sarcoma, or any of 
the various forms of adult connective tissue, as fibrolipoma, 
myxoma, chondroma, etc. 

A keloid is a fibrous tumor that forms usually from a scar. 
It is not confined to the seat of the original injury, but ex- 
tends somewhat into the surrounding tissues. Is usually 
smooth, and is most frequently seen in negroes. 

Molluscum fibrosum is a condition in which there is a non- 
inflammatory overgrowth of the fibrous structures of the nerves, 
particularly those of the skin and subcutaneous tissues. Such 
tumors may occur singly or be present by the thousand over all 
parts of the body. 

Epulis is a fibrous growth originating from the gum, usually 
at the site of diseased teeth. 

Myxoma is a benign tumor made up of mucous tissue. Is 
usually pale in color, round, lobulated, encapsulated, and 
feels semifluid. On section a thick, viscid fluid exudes. 

Microscopically spindle" and stellate cells with long proc- 
esses that anastomose are seen. In the meshes between the 
cells and processes is the mucous material. This substance is 
precipitated by acetic acid. 

They occur in sheaths of tendons and nerves and in nasal 
and pharyngeal polyps, and in combination with sarcoma. 
Mucoid growths forming from degeneration of fibromata are 
not true examples of myxomata. 

Lipoma is a benign tumor made up of fatty tissue. Is yellow 
in color, round, lobulated, encapsulated, and soft. May be 
very large. Microscopically the cells resemble ordinary fatty 
tissue, except in being considerably larger and the connective- 
tissue trabecular are also thicker than normal. Occurs most 
commonly in the subcutaneous tissue, in fasciae, and in synovial 
membranes. Is slow in growth and will frequently persist 
even if the individual is much emaciated. The blood-supply 



136 



TUMORS OR NEOPLASMS 



is poor, and such tumors may undergo various forms of infiltra- 
tion and degeneration, as calcification, ossification, necrosis, etc. 








(&*m (29L 



Fig. 46. — Myxomatous Fibroma of the Nasal Mucous Membrane 

(Diirck). 
Stellate connective-tissue cells joined together with protoplasmic proc- 
esses; the intercellular substance has become myxomatous and contains 
abundant masses of leukocytes. 

Occurs in combination with sarcoma, myxoma, fibroma, and 
angioma. 



OSTEOMA 



137 



Chondroma is a growth composed of either hyaline or fibrous 
cartilage. 

Arises from pre-existing cartilages, periosteum, or the medul- 
lary substance of the long bones. If it is found in localities 
where periosteum does not exist, as in the testicles and lungs, is 
called an enchondroma. 

Is hard, encapsulated, and lobulated. Is slow In growth, may 
persist for years, and become very large. 

Frequently undergoes mucoid degeneration and calcareous 
infiltration. 




Fig. 47. — Lipoma from the Region of the Shoulder with Relatively 
Small Fat Cells. (M. Fl. Ham.) X 300 (Ziegler). 



Is benign, but in combination with sarcoma may be quite 
malignant. Is also found in combination with lipoma, fibroma, 
and myxoma. An ecchondroma is a small overgrowth of carti- 
lage. Are found on the edges of the articular, laryngeal, and 
nasal cartilages. 

Osteoma is a tumor composed of bone. It may be a result 
of inflammatory processes of the periosteum or be a distinct 
new growth. 

If developing from a bone-forming tissue, is called an homol- 
ogous osteoma. 

If arising in a tissue that is not bone forming, is called a 



138 TUMORS OR NEOPLASMS 

heterologous osteoma. The latter are found in the meninges, 
lung, and parotid gland. 

An osteoma is a hard, bony, rounded, and more or less lobu- 
lated growth. Microscopically it presents quite typically the 
normal structure of bone. May be composed of spongy or 
compact new bone, osteoma spongiosum and osteoma durum. 




Fig. 48. — Hyaline Chondroma. Oc. 2; ob. 3 (McFarland). 



If the growth is small, circumscribed and flat, and arising 
from pre-existing bone, it is called an osteophyte. If irregular 
and projecting, an exostosis. 

Occurs most commonly at the epiphyses of long bones. 
Is benign. May be in combination with cartilage, fibrous 
tissue, fat, or sarcoma, in which latter case it is malignant, 



NEUROMA 139 

Myoma is a tumor composed of newly formed muscle-fibers. 
According as to whether the muscle is striped and voluntary, or 
unstriped and involuntary, we have the rhabdomyoma and the 
leiomyoma. 

The first is very uncommon, but occurs in the kidney, heart, 
and uterus. 

The latter occur frequently in the uterus and broad liga- 
ment, but may arise wherever there is involuntary muscle. 



Fig. 49. — Osteoma of the Lung. X 75 (Diirck). 

1, Bone-trabeculae; 2, fibrous interspaces not presenting the characters of 

medullary spaces. 

May be single or multiple. Are firm, round, lobulated growths, 
dark reddish in color. Microscopically they consist of elongated 
spindle cells, with rod-shaped nuclei collected in bundles that 
interlace in all directions. 

Are benign, slow of growth, and frequently undergo cystic 
or calcareous degeneration. The cysts contain mucus. 

Usually are in combination with fibroma. 

Neuroma is a tumor composed of nerve tissue. As the 



140 



TUMORS OR NEOPLASMS 



term has been applied to all growths found on nerves, two 
divisions are made: the true neuroma, which consists of nerve 
tissue; and the false neuroma, which consists of rlbroconnective 
tissue. 




Fig. 50. — Leiomyoma of the Uterus (Uterine Fibroid). Oc. 4; ob. 3 

(McFarland). 



The true is called a ganglionic neuroma when ganglionic 
nerve-cells are present; if nerve-fibers only are present, it is 
called a fibrillar neuroma. 

Hemangioma is a tumor made up of blood-vessels separated 
by a small amount of connective tissue. 

Angioma simplex or nevus when the vessels are small and 



ODONTOMA 141 

very much interwoven. To this class belong the reddish dis- 
colorations known as birth-marks. 

Cavernous angioma when the blood-spaces are large and 
separated by distinct fibrous bands. Resembles the struc- 
ture of the corpus cavernosum of the penis. 

Plexiform angioma when a group of more or less parallel 
blood-vessels become tortuous and widely dilated. 




Fig. 51. — Cavernous Angioma (Warren). 

Lymphangioma is a tumor caused by a dilatation of lymphatic 
vessels with an arrangement quite similar to that of the heman- 
gioma. 

An odontoma, according to Bland-Sutton, from whose work 
the following is taken, is a tumor composed of dental tissues 
in varying proportions and different degrees of development, 
arising from the teeth germs, or teeth still in the process of 
growth. 



142 



TUMORS OR NEOPLASMS 



The species of this genus are determined according to the 
part of the tooth germ concerned in their formation. 



i. Epithelial odontoma 

2. Follicular odontoma, 

3. Fibrous odontoma, 

4. Cementonia, 

5. Compound follicular 

odontoma, 

6. Radicular odontoma 

7. Composite odontoma 



= from the enamel organ. 



from the tooth follicle. 



= from the papilla. 

= from the whole germ. 



1. Epithelial odontoma occur, as a rule, in the mandible, but 
they have been observed in the maxilla. They have a fairly 




Fig. 52. — Epithelial Odontoma. Natural Size (Bland-Sutton). 



firm capsule, and in section display a collection of cysts of 
various shapes and sizes, but the openingsxrarely exceed 2 cm. 
in diameter. The cysts are separated by/ thin fibrous septa, 
sometimes ossified. The cavities contain a brown mucoid 
fluid which gives a reddish tint to the growing portions of the 
tumor. Histologically, an epithelial odontoma consists of 
branching and anastomosing columns of epithelium, portions 
of which form alveoli. The cells occupying the alveoli vary, 
the outer layer may be columnar, while the central cells de- 
generate and give rise to tissue resembling the stellate reticulum 
of an enamel organ. It may be that many of these tumors do 
not arise from the epithelial enamel organ, but from endothelium 
within the gums. 

Figures 52 to 61 inclusive are from "Tumours, Innocent and Malignant," by Sir John 
Bland-Sutton, F. R. C. S. 



ODONTOMA 



143 



2. Follicular odontoma comprise those swellings often called 
"dentigerous cysts," an inaccurate term. They arise commonly 






Wl 



■;-,-■ 

in 



1 - 

1 



: 



Fig. 53. — Microscopic Characters of an Epithelial Odontoma (Bland- 
Sutton) . 

in connection with teeth of the permanent set, and especially 
with the molars. Sometimes they attain large dimensions and 




Fig. 54. — A Follicular Odontoma from the Right Half of the 

Mandible of a Boy Aged Fourteen Years. 

Removed by Wormald, 1850 (Museum Royal College of Surgeons). 



produce great deformities, particularly when they arise in the 
upper jaws and happen to be bilateral. Occasionally they 
occur in connection with supernumerary teeth. The tumor 



144 



TUMORS OR NEOPLASMS 



consists of a wall of varying thickness, which represents an 
expanded tooth follicle; in some cases it is thin and crepitant, 
in others it may be as much as i cm. thick. The cavity of the 
cyst usually contains viscid fluid and the crown or the roof of an 





Fig. 55. — Follicular Odontomata from the Mandible (Bland-Sutton). 

imperfectly developed tooth. Occasionally the tooth is loose 
in the follicle, sometimes inverted, and often its root is trun- 
cated. Exceptionally the tooth is absent, or is represented by 
an ill-shaped denticle. The walls of the cyst always contain 




Fig. 56. — An Odontoma from the Mandible of a Rickety Youth Aged 

Nineteen Years. 

A, Denticle; B, portion of the outer wall of the jaw (Bland-Sutton). 

lime or osseous matter, the amount varying considerably. 
These tumors are not unknown in other animals, having been 
found in sheep, pigs, and porcupines. The amount of fluid 
in a follicular odontoma varies, and the size of the tumor de- 
pends in the main upon this. Sometimes the fluid may measure 



ODONTOMA 



145 



as much as 2 ounces, and this may lead to the wide separation 
of the inner and outer plates of the body of the mandible, and 
the odontoma may occupy the entire length of the bone. 




Fig. 57. — Odontoma Surround- Fig. 58. — The Odontoma in Sec- 

ing the Second Mandibular tion, Showing the Relation 

Molar of a Boy Aged Fif- of the Roots to the Tumor 

teen Years (Bland-Sutton). Tissue (Bland-Sutton). 



I H 





^M \ 




Fig. 59. — Fibrous Odontoma from a Goat. Natural Size (Bland- 
Sutton). 



3. Fibrous Odontoma. — In a developing tooth, a portion of 
the connective tissue in which it is embedded is found to be 



146 



TUMORS OR NEOPLASMS 



denser and more vascular than the rest; it also presents a fibril- 
lar arrangement. This condensed tissue is known as the tooth 
sac, and, when fully developed, presents an outer firm wall and 
an inner looser layer of tissue. At the root of the tooth the 
follicle wall blends with the dentin papilla, and is indistinguish- 
able from it. Before the tooth cuts the gum it is completely 
enclosed within this capsule. Under certain conditions this 
capsule becomes greatly increased in thickness and so thoroughly 
encysts the tooth that it is never erupted. Such thickened cap- 




Fig. 60. 



-Cementoma from a Horse. Half Natural Size (Museum 
Royal College of Surgeons). 



sules are mistaken for fibrous tumors, especially if the tooth 
be small and ill developed. Under the microscope they pre- 
sent a laminated appearance, with strata of calcareous matter. 
To these the term "fibrous odontomata" may be applied. As 
a rule they are multiple, four being by no means an unusual 
number. There is good reason to believe that rickets is respon- 
sible for some of these thickened capsules. 

4. Cementoma. — When the capsule of a tooth becomes en- 
larged, and these thick capsules ossify, the tooth will become 
embedded in a mass of cementum. To this form of odontoma 



ODONTOMA 147 

the name "cementoma" may be applied. Tumors of this char- 
acter occur most frequently in horses. The chief structural 
peculiarity is the presence, in enormous numbers, of large, 
richly branched openings. 

5. Compound Follicular Odontoma. — If the thickened capsule 
ossifies sporadically instead of uniformly, a curious condition 
is brought about, for the tumor will then contain a number of 
small fragments of cementum, or dentin, or even ill-shaped 
teeth (denticles) composed of three dental elements — cemen- 
tum, dentin, and enamel. The number of teeth or denticles 
varies greatly, and may reach a total of four hundred. 

6. Radicular odontoma is the term applied to those tumors 
which arise after the crown of the tooth has been completed, 
and while the roots are in the process of formation. As the 
crown of the tooth, when once formed, is unalterable, it natur- 
ally follows that should the root develop an odontoma, enamel 
cannot enter its composition; the tumor would consist of den- 
tin and cementum in varying proportions, these two tissues 
being the result of the activity of the papilla. The outer 
layer of the odontoma is composed of cementum; within this is 
a layer of dentin, and inside this is a nucleus of calcified pulp. 
It is probable that some radicular odontomata in man are due 
to inflammatory changes. 

7. Composite odontoma is a convenient term to apply to those 
hard tooth tumors which bear little or no resemblance in shape 
to teeth, but occur in the jaws, and consist of a disordered con- 
glomeration of enamel, dentin, and cementum. Such odontoma 
may be considered as arising from an abnormal growth of all the 
elements of a tooth germ, enamel organ, papilla, and follicle. 
Not only is this growth composite in that the tumor originates 
from all the elements of a tooth germ, but it is composite in 
another sense: many of these tumors are composed of two or 
more tooth germs indiscriminately fused. But they differ 
from the cementomata containing two or more teeth in the fact 
that the various parts of the teeth composing the mass are in- 
distinguishably mixed, whereas the individual teeth implicated 
in a cementoma can be clearly defined. It was long believed 
that composite odontomata occurred only in the mandible, but 



148 TUMORS OR NEOPLASMS 

it is clear not only that they arise as frequently in the maxillae, 
but that they attain a far larger size in the upper than in the 
lower jaw. 




Fig. 61. — Composite Odontoma. Natural Size (After Forget). 

Dental Cysts. — It occasionally happens that in extracting 
permanent teeth a small fibrous bag is found at the apex of 
the root, often no larger than an apple seed, though sometimes 
it may be as large as a bantam's egg, filled with fluid, and 
often containing crystals of cholesterin. These sacs, or dental 
cysts, occur in connection with the dead roots of mandibular 
and maxillary teeth, especially molars and premolars. They 
sometimes attain a considerable size in the upper jaw when 
they invade the antrum, and some of these cysts are sufficiently 
large to simulate an abscess of that cavity. Dental cysts are 
often bilateral and occasionally multiple. The constant asso- 
ciation of these cysts with the dead roots of permanent teeth 
has led many observers to regard them as pus- sacs with thick 
fibrous walls. Others, having demonstrated the existence of 
an epithelial lining in many of these cysts, believe that they 
arise in embryonal "rests/' known as "paradental epithelial 
remnants." 



PAPILLOMA 



149 



TUMORS OF EPITHELIAL TISSUES 

A papilloma is a benign tumor composed of projections of 
fibrous connective tissue that are covered by one or more layers 
of epithelium, either squamous or columnar in type. 

May be divided into the hard and the soft papilloma. 




Fig. 62. — Tuft of Papilloma of the Bladder (Stengel). 



The hard occur on the skin as warts, and when so situated 
are commonly pigmented; also around the genitalia as a result 
of constant irritation, in which situation they are known as 
'Venereal warts." Are also found on the true vocal cords in 
the larynx. Are covered by squamous epithelium which com- 
monly undergoes keratosis, a horny change. In this form the 
"pearly bodies" or "epithelial pearls" are frequently found. 
These are made up of cells concentrically arranged, many of 



150 TUMORS OR NEOPLASMS 

which have lost their nuclei and have become transformed into 
keratin. They are found only in squamous epithelium. 

Papilloma covered by squamous epithelium are frequently 
found in the urinary bladder, and, although histologically be- 
nign, they very frequently undergo malignant changes. 

The soft papilloma occur in the intestine, and are covered 
by columnar epithelium. This form quite frequently under- 
goes malignant transformation. 




*ftj 






" >> a^&Vy- 




I 



^ 



Fig. 63. — Alveolar Adenoma of the Mammary Gland. Oc. 2; ob. 9 

(McFarland). 

The connective-tissue stalks may be simple projections or 
very complicated, branching outgrowths. They contain blood- 
vessels and lymphatics. 

An adenoma is a tumor that in its structure resembles an 
epithelial gland. It is frequently very difficult to tell whether 
it is a true growth or only an enlargement of a normal gland. 

In the new growth the tissues, though arranged typically, 
do not carry on any useful function. The secretion may be 
imperfect or there may be no duct through which it can escape. 

Adenoma arise from epithelial glands, are circumscribed, 



ADENOMA 



151 



encapsulated and rounded, or nodular. Have been found in 
all glandular tissues. 

Microscopically they consist of a framework of connective 
tissue, the meshes of which are covered by one or two layers of 
epithelial cells that resemble in shape and size those of the 
normal glands. The important point that distinguishes these 
growths from malignant ones is the relation of the cells to the 




FlG. 64. — FlBRO-ADENOMA OF THE MAMMARY GLAND (CANALICULAR FORM). 

Oc. 2; ob. 3 (McFarland). 

basement membrane. In the benign adenoma the mem- 
brane is preserved and the cells show no tendency to invade 
the surrounding tissue. 

If the connective tissue and epithelium are in normal pro- 
portion the growth is called a simple adenoma; if the con- 
nective tissue predominates, a fibro-adenoma. 

If the tumor has a pedicle, it is known as an adenomatous 

polyp- 



152 TUMORS OR NEOPLASMS 

Through degenerations, particularly colloid or mucoid, an 
adenoma may become very large through cystic formation. 
It is then called an adenocystoma. 

If villi extend into the acini in the above form the growth is 
called an adenocystoma papilliferum. 

Hypernephroma are tumors that resemble the cortical 
portion of the adrenal gland. They probably arise from mis- 
placed portions of adrenal tissue, and, as such "rests" consist 



ft -/.>?.* - ®<® 



; ■-- ^*£&WT 






\; 












• 
up pi 




Fig. 65. — Adrenal Tumor from the Kidney (Hypernephroma) (Diirck). 

1, Large polygonal cells, containing an abundance of fat and arranged in 

tubes; 2, connective-tissue cells in the scanty stroma. 

of only cortical elements, these tumors do not resemble the 
medulla of the gland nor do they contain epinephrin. Are 
found most commonly in the upper hole of the kidney, liver, 
broad ligament, and in other abdominal tissues. 

Although commonly benign and encapsulated, they may 
take on a malignant change, infiltrate, and give rise to metas- 
tases by means of the blood-vessels. 



CARCINOMA 153 

The cells are large and vesicular, with large round, cen- 
trally placed nuclei. The connective-tissue framework is 
very slight. Dilated capillaries and areas of hemorrhage are 
common. 

Glioma are growths composed of neuroglia or nervous con- 
nective tissue. As they arise from the epiblast, they cannot 
be classified with the mesoblastic tumors. 

Are usually small, reddish in color, and not distinctly limited 
from surrounding tissues. 

Microscopically they are composed of cells with large nuclei 
and with long fine processes. 

Blood-vessels may be numerous and many areas of hemor- 
rhage present. 

Are benign and slow growing. 

CARCINOMA 

A carcinoma is a malignant tumor of epithelial origin. It 
is characterized by a marked proliferation of epithelium with 
infiltration into the surrounding tissues. 

The epithelium is arranged atypically in a supporting frame- 
work made up of adult connective tissue 

The epithelial cells are not characteristic of the growth, 
but they differ in some respects from the normal type. The 
diagnosis of carcinoma cannot be made from the cell, as there 
is no distinct cancer cell. The general arrangement of epi- 
thelium and connective tissue must be taken into considera- 
tion. 

The carcinomatous epithelium frequently consists of cells 
many times larger than normal. Their nuclei may be un- 
usually large, vesicular, and show a peculiar affinity for nuclear 
stains, a condition called hypcrchromatosis. 

They may divide by an atypical mitosis and give rise to 
peculiar arrangements of the chromatin. These cells mul- 
tiply rapidly, and, though at first round, they may become 
almost any shape on account of the mutual pressure exerted. 

In some cases giant cells occur. Tumors of this variety 
differ greatly in size, shape, color, and density. 



154 



TUMORS OR NEOPLASMS 



Carcinoma are composed of two types of tissue, epithe- 
lial and connective,, cells and stroma. According to the one 
that predominates, carcinoma are called medullary when the 
cells are more numerous; scirrhus when the tumor is rich in 
connective tissue. 

The first is soft; the second, hard. 










Fig. 66. — Carcinoma of Mammary Gland (Mallory). 
Medullary type of growth. Slight tendency to the formation of gland 

lumina. 

Well-developed blood-vessels and lymphatics are found 
in the stroma, which is most likely derived chiefly from pre- 
existing connective tissue, but a certain amount is probably 
newly formed. Elastic fibers are present in the infiltrating 
portion of the growth, but they are fragments of fibers pre- 
existing in the invaded tissue. The cellular elements originate 
from the epithelium normal to the part involved, and fre- 
quently retain the characteristics of the primary cell. 



CARCINOMA 155 

The more closely connected it is with the original cell, the 
more does the carcinoma cell resemble it. The further away 
it is, the greater is the variation. There is then a tendency 
to revert to the round, undifferentiated, embryonal type. Be- 
tween the cells no fibrillary substance is found. 

In carcinoma the cells frequently undergo degeneration, 
and usually of a form peculiar to the parent tissue. If it 









V^ — ~ ■---■ • - ^ 




Fig. 67. — Scirrhous Carcinoma of Breast (Mallory). 
Alveoli of epithelial cells small; stroma abundant. 

arose from squamous epithelium, keratin is found; colloid or 
mucoid material if derived from mucous membranes. The 
tumor may break down and undergo a fatty change, most 
common in the mammary gland. 

A carcinoma may become infected and show marked in- 
flammatory changes which may be so great as to somewhat 
disguise the true character of the growth. There will be an 
infiltration of the tissues with leukocytes. 



156 



TUMORS OR NEOPLASMS 



Microscopically a carcinoma consists of columns of cells 
running in all directions, separated from one another by fibrous 
tissues. These columns give the appearance of alveoli filled 
with epithelium. The columns are branched into numerous 
subdivisions, giving a complicated root-like structure. 

As the tumor grows these cells infiltrate and ramify in all 
directions, occupying usually the lymphatic spaces. Along 




Fig. 68. — Carcinoma op Mammary Gland (Mallory and Wolbach). 
Extension of tumor through a lymphatic in fat tissue. 



the advancing border there is a more or less well-marked zone 
of round-cell infiltration. 

As there is no intracellular substance, the cells easily break 
away from the main mass and are carried to the neighboring 
lymph-nodes. This may take place very early and give rise 
to extensive metastasis. These secondary growths are usually 
similar in character to the primary. 



SQUAMOUS EPITHELIOMA 



157 



Extension to distant tissues may be due to permeation. 
According to this theory there is a continuous growth of cancer 
cells along the lymphatics of the deeper fascia, with wide- 
spread involvement. 

A squamous epithelioma is a carcinoma that has arisen 
from a surface covered by stratified epithelium such as skin 




Fig. 69. — Squamous Epithelioma (McFarland). 
a, Epithelial masses; b, epithelial pearls; c, connective tissue: d, capillary 

blood-vessels. 



and certain mucous membranes. It occurs most commonly 
on the cervix, the skin of the face, penis, vagina, and esoph- 
agus, especially wherever there is a junction of skin and mucous 
surfaces. 

It makes its appearance as an indurated mass in which 
ulceration takes place rapidly and exposes a circular surface 



158 TUMORS OR NEOPLASMS 

with raised, hard edges. Sometimes it looks at first like a 
small wart. 

Columns of these cells penetrate the tissues and on account 
of pressure arrange themselves in successive layers, the inner 
ones being almost flat and confined, forming the epithelial 
pearls. Hyperkeratosis is the term used to indicate the corni- 
fication. 

The presence of these pearls does not indicate that the tumor 
is necessarily malignant; they mean that the growth was de- 
rived from squamous epithelium. They are also not always 
found in squamous epithelioma ta. The growth may have been 
so rapid as not to have allowed cornification to take place. As 
the cells infiltrate the surrounding tissue, there is a well-marked 
border zone of round cell infiltration, and the elastic tissue, 
as a rule, shows various forms of degeneration. 

The cells are usually quite large, and may show numerous 
"prickles." 

This form of carcinoma differs greatly in its malignancy. 
Some may exist for several years without showing much tend- 
ency to spread, but may suddenly grow and cause extensive 
destruction of tissue, with subsequent death of the patient. 
They recur on removal, and give metastasis by the lymphatics. 

X-Ray Carcinoma. — As a result of long-continued exposure 
to the #-ray, chronic dermatitis very commonly develops. The 
superficial cells become necrotic, but in addition there is an in- 
volvement of deeper structures. Necrotic foci occur in the co- 
rium, probably due to vascular disturbances, such as a narrowing 
of the lumen of the vessels due to a proliferation of the endothe- 
lium. These deeper lesions may remain quiescent, but eventu- 
ally the epidermis undergoes a downward proliferation, invades 
these foci, takes on an infiltrating character, and may give rise to 
very extensive metastases. The fingers and hands are usually 
the site of the primary lesion or lesions. The histologic struc- 
ture of these growths is that of the squamous epithelioma. 

Rodent ulcer or carcinoma basocellulare arises from the basal 
cells of the epidermis, particularly from those cells in the hair- 
follicles. Are most common in the region of the eyes and nose, 
usually occurring in men. 



ADENOCARCINOMA 



159 



For many years — from three to twelve or more — there may 
be present a smooth, rounded nodule about the size of a pea. 
This may then break down and form an ulcer with rounded, 
smooth, and firm pearly gray edges. The ulceration may 
extend widely, bringing about extreme destruction of all the 
invaded tissues. It very rarely undergoes cicatrization, and 
seldom if ever gives metastasis or involves lymph-nodes. The 




Fig. 70. — Rodent Ulcer (Mallory) . 



cell nests have a peculiar roset form, due to the short, blunt 
projections of cells at the periphery. The nuclei are, as a rule, 
long, narrow and spindle shaped, and do not stain deeply. 
At the periphery of the cell nests the nuclei are arranged some- 
what radially. 

It is usually single, but may be multiple and may continue 
for many years — three to twenty-four. 

An adenocarcinoma is a cancer in which the glandular struc- 



TUMORS OR NEOPLASMS 




■er.fi* 



Fig. 71. — Adenocarcinoma of the Body of the Uterus (Cullen). 
0, May be likened to a main stem from which arise numerous secondary 
stems, which in turn give off delicate terminals, consisting entirely of epi- 



ADENOCARCINOMA l6l 

ture is to a great extent preserved, but the epithelium has 
taken on a proliferative growth. It either breaks through the 
basement membrane or else tills up the acini with numerous 
layers of cells. It is commonly found in the stomach, intes- 
tines, and uterus. Grows rapidly, gives metastasis, and quickly 
proves fatal. 

The development of carcinoma differs greatly in different 
people. In some cases a continued mild irritation may pre- 
cede. The growth may be very slow, but if for some reason 
there is an increase in the nutrition, as in the pregnant uterus, 
it may suddenly become rapid. 

If the growth is rapid and metastasis extensive, the health 
of the patient suffers and cachexia develops. This may be 
the result of pain, of suppurative conditions, or from the ab- 
sorption of toxic substances resulting from the disturbance of 
metabolism. 

The etiology of carcinoma is still obscure. Heredity is ap- 
parently clear in many cases as a predisposing cause. 

Age is of importance, the majority of cases appearing after 
thirty-five, a time when the resisting power of the tissues is 
beginning to diminish. 

Carcinoma is more common in women than in men. In 
women it is in the genital organs; in men, in the intestinal tract. 

Irritation and injury seem to at least be of some importance 
as exciting causes, although in themselves it is doubtful if they 
can give rise to a carcinoma. 

Loss of resistance of the connective-tissue stroma has been 
advanced, but does not seem logical. Many observers have 
tried to prove that these growths are infectious processes, 
the results of parasitic activity. Many cellular inclusions 
resembling protozoa have been found, but the general opinion 

thelial cells. The glands may be divided into groups a, b, c, d, and e, by the 
stems of stroma. /, g, and h. The stems are covered by several layers of 
cylindric epithelium, while projecting into the gland cavities are long slender 
ingrowths of epithelium, devoid of stroma, as seen in i. Very delicate in- 
growths consisting merely of two layers of epithelium are seen at k and k. 
At I the epithelium is several layers in thickness, and at m many layers with 
leukocytes. The arborescent character of the growth and peculiar gland 
grouping are characteristic of adenocarcinoma. 



1 62 TUMORS OR NEOPLASMS 

at present is that these bodies are nothing more than degen- 
erated cells or secretions of cells. Experiments to prove the 
infectious nature of carcinomata have not been generally suc- 
cessful. The transplantation of cancer tissue into a normal 
individual has failed. But when placed in another situa- 
tion in the person from whom the tissue was excised growth 
has followed. This has frequently been considered proof of 
the parasitic nature. It probably means nothing more than 




Fig. 72. — Syncytial Masses Invading a Venous Channel in a Case 
of Deciduoma Malignum (J. Whitridge Williams). 

that the pieces of tissue have found surroundings favoring their 
growth; a condition such as occurs in skin-grafting. 

Bacteria, protozoa, sporozoa, gregarinas, blastomycetes, 
amebae, and fungi have all been suggested as the cause. These 
claims, however, rest upon the form of the bodies and their 
staining properties, not upon cultivation and inoculation. Until 
these latter can be carried out the parasite theory must re- 
main unproved. 



CHORIO-EPITHELIOMA 1 63 

CHORIO-EPITHELIOMA 

The following discussion and classification is taken from 
Adami and McCrae: 

To properly understand the formation of the chorio-epithe- 
lioma it will be necessary to review briefly the origin of the 
fetal placenta. This structure, arising from chorionic villi, 
finally develops a vascular mesoblastic core covered by epiblast. 
The outer cells of the fetal chorion erode into the mucous 
membranes of the uterus. Normally these cells, when they 
have penetrated into the sinuses, have done their work, and 
the outer layer becomes inactive, fuses, and forms the syncyt- 
ium. Sometimes in cases of abortion these placental changes, 
usually complete by the time of full term, have not yet oc- 
curred, and when the immature fetus is expelled, there remain 
chorionic cells which have not degenerated and are still actively 
growing. These constitute the evil agent; they continue then- 
growth in the uterus and form a neoplasm. 

Placental Mole. — In some instances the fetus may die, be 
absorbed, and leave the placenta and membranes grafted upon 
the uterus in the form of an irregular fleshy mass, prone to 
hemorrhage and to putrefaction. On the other hand, the 
chorionic villi, being nourished by maternal blood, may grow 
actively and absorb fluid so that a villus becomes a vesicle or 
a series of vesicles. These may be large or small, due to disten- 
tion by an edematous mucoid fluid. These vesicles may 
eventually take up as much room as a full-term fetus. Such 
an edematous mass of vesicles is known as a hydatid mole. 

Chorio-epithelioma. — Such a hydatid mole as above de- 
scribed may pass beyond the usual growth and fill the uterine 
sinuses with polypoid masses, the so-called destructive placental 
polyp. The outer surface of the villus, consisting of fetal 
epiderm, becomes fused to form syncytium, which is made of 
deeply staining cells whose bodies have fused, the mass thus 
being multinuclear. Below the syncytial layer the cells of 
Langhans' layer remain unfused, individual, and less deeply 
staining. The syncytium possesses erosive and phagocytic 
properties, and it is these masses of cells that tend to be swept 



164 TUMORS OR NEOPLASMS 

away in the blood of the maternal sinuses and to be deposited 
in the capillaries of the lung and elsewhere. 

Chorio-epithelioma Malignum. — This term is applied to a 
neoplasm that is entirely cellular, formed of large actively 
vegetative cells growing entirely within the vessels, not requir- 
ing an individual blood-supply by vessels of its own, not cap- 
sulated, liable to induce hemorrhage by erosion of the vessel 
walls, and very readily tending to have particles carried away 
to grow elsewhere. Such a tumor generally occurs shortly 
after an interrupted pregnancy, but may not occur for years 
after an abortion with no intervening pregnancy. Microscop- 
ically, various cells are seen. Very large ones containing many 
large nuclei, rich in chromatin, are formed by direct division. 
Others, much smaller, with single well-formed nuclei. Some 
that resemble lymphocytes, and all kinds of forms resembling 
the above types more or less closely. In places there may be 
found long narrow strands of protoplasm containing nuclei, but 
showing no division into individual cells, syncytium. Clinically, 
these tumors show great variations in malignancy, although 
microscopically their structure may be similar. 

TERATOMA 

Under this heading are included those tumors which have a 
tendency to the formation not only of irregular cell masses, 
but also of fully formed organs, such as brain, teeth, skin, hair, 
bone, or secreting glands. Such growths may be due to the 
development of two germinal areas on one germinal vesicle, 
giving rise to double monsters, one of which undergoes inclu- 
sion in the other — fetal inclusion. They may result from the 
displacement of totipotential cells — those capable of giving 
origin to an individual — which become included in the growing 
organism. These cells may develop early and grow elaborately, 
giving rise to inclusions recognizable at birth. They may lie 
latent and at a subsequent time grow actively as abdominal 
inclusions, teratoma of the genital glands, and certain mixed 
tumors. 

Dermoid cysts, ovarian dermoids are the most common of 
the teratoma. The cyst cavity is lined by squamous epi- 



DERMOID CYSTS, OVARIAN DERMOIDS 



16: 



thelium in which are found sweat and sebaceous glands. Within 
the cavity is usually a varying amount of fatty material in 
which are masses of hair. In the wall of the cyst are found 
masses of bone to which teeth, usually but poorly formed, are 
attached. In some instances the extremities and genitalia 
have been seen. 




Fig. 73. — Teeth from Ovarian Dermoid (From Coplin after Roberts). 
An irregular branching piece of bone contained in a dermoid cyst of 
the ovary, in which are implanted well-formed teeth: 1, 1, Bony mass; 
2, a tooth resembling a canine of the first dentition; 3, 3, 3, teeth re- 
sembling molars. 



Somewhat similar growths may be found in those parts of 
the body where fetal clefts have united and in the median 
fissures of the body. 

There is another type, the sporadic teratoma, which grow 
in regions bearing no relationship to the fissures, to the poles 
of the body, or to the generative glands, as in the anterior 



1 66 TUMORS OR NEOPLASMS 

mediastinum and the abdomen. These are probably due to 
the development of a misplaced totipotential cell. They 
generally consist of tissues from all three germinal layers. 
Sometimes the tissues are of adult appearance and of limited 
growth. More frequently they appear about puberty, grow 
rapidly, and tend to form secondary tumors. 

CYSTS 

A cyst is a collection of a fluid or semifluid substance con- 
tained within a connective-tissue wall lined by epithelium or 
endothelium. The contained material may be serous, mucous, 
or purulent if infection has occurred. 

Cysts may be either single or multilocular. The latter when 
divided into numerous compartments by fibrous partitions. 
These division walls may break down and convert a multi- 
locular into a simple cyst. 

Cysts may be divided into the following: 

i . Retention cysts, resulting from an obstruction to the out- 
flow of the secretion of a gland. 

2. Exudation cysts, those formed by an increase of fluid 
in a closed cavity, as in the tunica vaginalis. 

3. Necrotic or liquefaction cysts result from the breaking 
down of the central portion of solid tumors. 

4. Parasitic cysts may occur on account of an inflamma- 
tory reaction around the parasite, or may be formed directly 
by it in its development. 

5. Dermoid cysts belong to the teratomata, where they are 
described. 

6. Cystoma, a cyst of neoplastic formation. They most fre- 
quently occur in the ovary and are multilocular. 



CHAPTER X 

SPECIAL PATHOLOGY OF THE MOUTH 

Malformations of the lips and cheeks are usually associated 
with defective formation of the bones of the mouth. The entire 
process is usually due to an arrest of development or a failure 
of the branchial arches to fuse normally. 

i. The lower jaw is absent; the upper jaw and hard palate 
are small and imperfectly formed; the temporal bones nearly 
touch in the median line. The lower part of the face, there- 
fore, is lacking; the mouth is absent or small and closed poste- 
riorly; the tongue is absent. 

2. The face remains in its early fetal condition of a large 
cleft; the mouth and nose form one cavity; the orbits may be 
united in the same cavity. 

3. There is a cleft in the upper lip, upper jaw, and hard 
palate. The cleft corresponds to the point of junction of the 
processes of the superior maxilla with the intermaxillary bone; 
consequently it occurs to one or the other side of the midline. 
There may be one cleft or two, one on either side of the inter- 
maxillary bone. The cleft involves the lip alone — harelip — 
or the lip and superior maxilla, or the lip, maxilla, and palate. 
There may be a single or a double cleft in the palate, and the 
cleft may involve either the hard or soft palate or both. If 
there are two clefts of the lip and maxilla, the portion of lip 
and bone between them may be small or entirely absent, so as 
to leave a large open space. The soft palate may be absent 
entirely. 

4. Rarely there is a cleft involving the middle of the lower 
lip and sometimes extending into the lower jaw. 

5. Either the inferior or the superior or both maxillary bones 
may be abnormally small. 

167 



1 68 SPECIAL PATHOLOGY OF THE MOUTH 

6. The edges of the lips may be partly or completely joined 
together. The opening of the mouth may be only a round 
hole. 

7. The lips may be absent or imperfectly developed. 

8. The corners of the mouth may be prolonged by clefts in 
the cheek reaching nearly to the ears. 

Anemia of the mucous membranes of the mouth and lips 
is commonly seen in cases of general anemia, and is a well-recog- 
nized symptom. 

Hyperemia of the active type is found in the various in- 
flammations and as an early symptom in certain infectious 
diseases. Passive hyperemia occurs in the general congestion 
of chronic lung and heart disease. Actual bleeding is found in 
scurvy and purpura, and sometimes in the infectious fevers. 

Inflammation, Stomatitis. — Inflammation of the mucous 
membranes of the mouth results from many causes, but par- 
ticularly from local infection by bacteria. 

Catarrhal stomatitis is most frequent in children, and may 
result from a great variety of local and general disturbances. 
The action of irritants, such as hot liquids, chemicals, decaying 
teeth, or from a depressed condition of the general system. 
The congestion and swelling of the mucous membrane may be 
well marked, and in chronic cases there is frequently a thicken- 
ing of the mucous membrane with the formation of whitish 
areas. The mucous glands may enlarge and form small cysts. 
There is usually an increased amount of mucous secretion, but 
sometimes the membranes may be unnaturally dry. . In addi- 
tion to the hyperemia and local edema there may be prolifera- 
tion, exfoliation, and degeneration of the epithelium. There 
may also be some infiltration of leukocytes. 

Ulcerative stomatitis is usually found in children who are not 
well nourished. It occurs in malnutrition, tuberculosis, and in 
other chronic conditions, also in mineral poisonings, particu- 
larly by mercury and phosphorus. It usually begins at the 
margin of the gums of the lower jaw and extends to the cheeks 
and tongue. The gums become red and swollen and even 
hemorrhagic at the junction with the teeth, and change into a 
soft necrotic mass that bleeds easily. The epithelium is de- 



INFLAMMATION, STOMATITIS 



169 



stroyed and deep ulcers form; suppuration may ensue and the 
teeth become so loosened that they fall out, the jaw bone be- 
comes exposed, infection occurs, and necrosis of the jaw follows. 
There is also an increased flow of saliva, accompanied by a bad 
odor. At the same time the general health is more or less 
affected, the patient becomes pale and loses weight. Mercury 
in too large doses or in small doses continued for too long a 
time may be the cause, and the condition is known as salivation. 




Fig. 74. — Thrush Fungus, Epithelial Cells, and Leukocytes from a 
Child Suffering from Ulcerative Stomatitis (Boston). 



Aphthous stomatitis occurs usually in children who are in 
poor physical condition or who have not been taught how to 
take care of the mouth. It may occur in adults who are not 
well. On the mucous membranes of the mouth there appear 
small whitish spots surrounded by an inflammatory zone. 
These areas consist of degenerated epithelium and fibrin 
which may at times exfoliate, leaving small ulcers. This con- 
dition may last for some time, the exudate finally being absorbed 
and the epithelium regenerating. 

Thrush is the form of micro-organismal stomatitis caused 



170 



SPECIAL PATHOLOGY OF THE MOUTH 



by the Oidiutn albicans which involves those structures covered 
by squamous epithelium. This fungus does not seem to attack 
the normal mucous membranes, but becomes engrafted upon 
a mucosa that is the seat of some inflammatory disturbance. 
It usually occurs in marasmatic infants, but may be present 
in adults after or during acute fevers or chronic diseases with 
debility. The tongue is involved most frequently primarily, 

but secondary infections may 
develop through contact. 
There is at first a diffuse red- 
dening of the mucous mem- 
brane, then the formation of 
patches of a shining, whitish 
false membrane that, although 
superficial, adheres at first 
rather tightly to the underly- 
ing tissue, but finally becomes 
looser. The membranous spots 
vary in size; at first the diam- 
eter rarely exceeds 4 to 5 mm. 
The patches may coalesce, 
forming large areas of a 
pseudomembrane that is com- 
posed of desquamated epithe- 
lium, extraneous organisms, 
and parasitic threads. If the 
membrane is removed, it soon 
reappears. The disease may 
spread from the tongue to 
the pharynx and the esophagus, and it has been known to ex- 
tend into the stomach and bronchi. 

The Oi'dium albicans is a budding fungus resembling the 
yeast and forms long myceliae. It can be cultivated upon 
acid media that contain sugar, but longer threads form when it 
is grown on alkaline media. 

Gangrenous stomatitis, or noma, is a rapid necrotic process 
involving the mucous membrane of the cheek. It occurs in 
children between two and twelve years of age whose general 




Fig. 



(Oidium) 



75. — Endomyces 
Albicans. 
a, Filaments from a patch of 
thrush; b, terminal chlamydospores; 
c, asci and ascospores. 



INFLAMMATION, STOMATITIS 171 

condition is extremely poor, either as the result of chronic or 
severe acute disease; it usually follows some of the acute in- 
fectious processes, particularly measles. It begins near the 
angle of the lip on the buccal surface as a livid area, at first 
hard and edematous, but rapidly becoming softer and gan- 
grenous. Penetration through to the skin may occur or the 
process may remain localized in the mucous membrane and 
underlying tissues. By the time the skin is involved vesicles 
are formed and the tissue soon breaks down into a foul-smelling 




Fig. 76. — Spiroch.eta Vincenti from Case of Ulcerative Stomatitis 
(X 1200) (Todd). 

mass. Hemorrhage is infrequent, probably the result of ex- 
tensive thrombosis. Death from exhaustion and secondary 
infection usually follows. The slough may separate and the 
patient recover, with commonly marked deformity from the 
cicatrization. Although more common in female children, 
noma may occur in either sex at any age. No specific cause 
for this condition has been discovered. Many forms of bacteria 
have been found, but the more common type found is a spirillum 
or spirochete, possibly Vincent's fusiform organism. 



172 SPECIAL PATHOLOGY OF THE MOUTH 

Syphilitic stomatitis may occur either as the primary chancre 
or, what is more common, as the secondary mucous patch. The 
primary lesion may appear on the lip, tongue, or tonsil in either 
a soft or an indurated form, and is accompanied by enlargement 
of the lymph-nodes. Mucous patches may occur on any part 
of the mucous membrane, but are commonest on the lips and 
palate. They are irregular, superficial ulcers, frequently cov- 
ered by a thin grayish pseudomembrane. They are painful, 
and the condition is usually associated with increased flow of 
saliva and a bad odor. Sometimes the local inflammatory 
condition gives rise to considerable thickening of the mucosa, 
this membrane becoming white or bluish-white in color. The 
area is usually small and is called leukoplakia; it may undergo 
eventually a malignant change, becoming cancerous. In the 
tertiary stage gumma may be found in the tongue or in the 
palate. They are generally small and are prone to undergo 
softening, with ulceration and subsequent cicatrization. 

Tuberculosis may rarely be primary, but is usually secondary 
to infection from tuberculosis of the larynx or pharynx or by 
infected sputum. The posterior portion of the tongue is usually 
involved, small nodular tubercles of a yellowish-red color 
appearing. These soon degenerate, forming ulcers with thick- 
ened edges. The lesions may very closely resemble epithelioma. 

Actinomycosis may result from the infection of an abraded 
surface by the fungus. It generally gains entrance to the 
alveolar portion of the jaw by way of carious teeth. The 
process is, as a rule, a slow one of swelling, with destruction of 
the adjoining tissues. There may accompany it a widespread 
involvement of the lymphatic nodes of the neck and jaw. 

Oral Sepsis. — Under this term are included the various 
inflammatory conditions affecting the mouth and attended by 
manifest infection. According to Coplin, many believe that, 
in addition to the purely local influence exerted by septic 
processes involving the oral mucosa and gums (gingivitis), 
important secondary manifestations are not uncommon. Al- 
veolar abscess, periostitis, suppurative inflammation of the 
antrum and nasal sinuses, tonsils, pharynx, and middle ear 
may be secondary to lesions primary in the buccal mucosa. 



GLOSSITIS 173 

Local infection traveling by the lymphatics may implicate the 
submaxillary and anterior cervical lymph-nodes. Inflamma- 
tion of the gastro-intestinal mucosa may be caused by pyogenic 
organisms which are primarily colonized in the mouth. Infec- 
tion of the blood, manifested by pleurisy and other forms of 
serositis and even ulcerative endocarditis, may have a similar 
origin. Some contend that pernicious anemia is the result of 
oral sepsis. A form of alveolar inflammation, characterized 
by suppuration extending deeply into the sockets of the teeth, 
and called pyorrhea, or pyorrhea alveolar is, sometimes causes an 
acute suppurative inflammation, or occasionally necrosis, of 
the adjacent bone. 

Glossitis, or inflammation of the tongue, occurs either in a 
superficial or a deep form and may be acute or chronic, diffuse 
or circumscribed. It may follow marked intestinal disorders 
or be the result of local irritations, such as the sharp edge of an 
ulcerated tooth or an ill-fitting dental plate. The surface of the 
tongue becomes white or brown, due to the degenerated epi- 
thelium, bacteria, and particles of food. It may become dry, 
hard, and fissured. If the superficial glossitis becomes chronic, 
local thickenings of the mucous membrane are formed. These 
are irregular, slightly elevated, whitish patches, which may 
spread and coalesce. This is known as leukoplakia, or psoriasis 
linguae, and in the great majority of instances is probably syph- 
ilitic in origin. Occasionally the thickened epithelium may 
desquamate and leave an ulcer. Quite frequently secondary 
cancer (epithelioma) develops at the site of the lesion. 

The deeper inflammations of the tongue usually result from 
injury and infection. The organ becomes swollen, painful, and 
infiltrated by leukocytes; small abscesses may form. This 
condition is usually accompanied by some degeneration and 
atrophy of the muscles. 

One form of inflammation of the tongue is known as melano- 
glossia, black tongue. The epithelium upon the papillae, 
particularly the filiform variety, becomes greatly increased and 
gives rise to a hairy appearance. The color may be due to an 
increase of pigment in the epithelium or to a fungus mixed with 
which are particles of food and bacteria. 



174 SPECIAL PATHOLOGY OF THE MOUTH 

Tumors of many kinds are found within the mouth. Of 
the connective-tissue forms, lipoma, fibroma, myxoma, and 
sarcoma occur; also lymphangioma and hemangioma. Adenoma 
and carcinoma of the squamous type are found. Sarcoma gen- 
erally appears upon the gums near the roots of the teeth and 
is known as an epulis; is usually composed chiefly of spindle 
cells with giant cells more or less numerous. The term "epulis" 
may be applied to pure fibroma. Carcinoma is, as a rule, 
present in the form of the squamous epithelioma. It is found 
most commonly on the tongue, near the tip, but to one side. 
It frequently occurs at the site of a long-continued ulceration 
from a carious tooth. There appears a circumscribed, hard 
swelling which soon breaks down and ulcerates rapidly. The 
neighboring cheek and larynx may soon be involved and metas- 
tases occur in the cervical and submaxillary lymph-nodes. 
The growth is usually rapid and, if excised, quickly returns. 
This lesion frequently resembles syphilitic conditions and occa- 
sions difficulty in making a diagnosis. 

Cysts may result from obstruction to the ducts of the mucous 
or salivary glands. A ranula is a cystic dilatation of Nuhn's 
glands situated under the tip of the tongue, which may be dis- 
placed backward and upward. A thick viscid fluid fills the 
cavity. Dermoid cysts and cysts of the embryonal branchial 
clefts may involve the mouth. 

Macroglossia, thickening of the tongue, and macrocheilia, thick- 
ening of the lips, result from a lymphangioma. The lymphatic 
spaces are much distended and contain liquid and lymphoid 
cells. This condition is generally congenital, being due to a 
deficiency in the amount of thyroid secretion. It occurs chiefly 
in cretins. 

THE TONSILS 

Anemia and hyperemia occur here just as elsewhere. Active 
hyperemia as a beginning of inflammation; passive, in chronic 
heart and lung disease, in which cases the veins may be dis- 
tinctly varicose. Edema is found in connection with inflam- 
mation and ulceration, and may be quite marked. Hemor- 
rhage may occur in purpura and in severe infectious fevers, 



TONSILLITIS 175 

as well as being the result of direct injury. At times the 
blood may form quite a tumor between the layers of the soft 
tonsil. 

Tonsillitis, or inflammation of the tonsil, may be either 
acute or chronic. Acute tonsillitis may be symptomatic either 
of various diseases or it may be a true local primary condition 
as a consequence of direct infection. According to the degree of 
inflammation, this condition may be catarrhal, lacunar or fol- 
licular, and phlegmonous. In the catarrhal type the tonsils 
are somewhat swollen and reddened and the condition is 
usually an accompaniment of a catarrhal pharyngitis. The 
lacunar or follicular form is characterized by the presence of 
many small yellowish-white spots over the surface of the 
tonsil. Each spot represents a follicle that has become rilled 
with an exudate made up of degenerated epithelium and bac- 
teria, as staphylococci, streptococci, pneumococci, or tubercle 
bacilli. The exudate from the lacunae may extend over the 
surface of the tonsil, forming a covering that resembles the 
diphtheric pseudomembrane. The exudate within the lacunae 
may become dry and lime salts be deposited. If the infection 
passes through the crypts to the deeper tissues, phlegmonous 
tonsillitis may result. In this there is abscess formation as 
well as round-cell infiltration. These collections of pus may 
discharge into the mouth, open into the larynx or even involve 
the large vessels of the neck, perforation of the carotid having 
occurred. 

Recent investigations into the bacteriology of tonsillitis 
indicate that many of the general infections of the body are 
secondary to the entrance of the organisms through the tonsils. 
The acute inflammatory rheumatic conditions, accompanied 
by severe involvement of the joints and of the heart, are evi- 
dently the result of tonsillar invasion. These structures are 
also suspected of being the portals by means of which the 
tubercle bacilli gain entrance into the cervical lymph-nodes. 

In chronic tonsillitis there is an increase in the size of the 
tonsils, due not only to a hyperplasia of the connective-tissue 
septa and reticulum, but also to an increase in the lymphoid 
follicles themselves. The tonsils may become so hypertrophic 



176 SPECIAL PATHOLOGY OF THE MOUTH 

as to almost meet in the middle line, and by so doing cause ob- 
struction to breathing and swallowing. 

This form is frequently accompanied by marked disturbances 
of the general health and development. It is often present in 
children, and as a result they breathe with their mouths open; 
their digestion is often impaired and their mentality may be 
distinctly below normal. Another common result of this 
condition is an interference with the proper development of the 
upper jaw and nasal cavities. The upper jaw may be distinctly 
narrowed, thus causing more or less deformity with displace- 
ment and irregularities of the teeth. The enlarged tonsils 
should be removed at an early age before the bony tissues have 
become so hardened as to prevent corrective measures. 

Instead of the above hypertrophic form, the involvement 
may be confined to the lacunae, which are wider and deeper 
than normal. They become filled with an exudate that through 
decomposition can give rise to inflammatory processes in ad- 
jacent tissues. 

Tonsillitis leptothricia is caused by infection of the tonsils 
by the Leptothrix buccalis. It usually occurs in those in poor 
condition, but may be found in strong, well-nourished indi- 
viduals. Over the surface of the tonsil are numerous spots 
covered by a thick, dense, dry, whitish exudate that is com- 
posed of masses of threads of the leptothrix. This is firmly 
adherent to the crypts and is removed with difficulty. It 
usually involves other portions of the pharynx, but does not 
occasion much inflammation in the surrounding tissues. It 
tends to run a chronic course, not yielding readily to treat- 
ment. 

Tuberculosis of the tonsils is not uncommon. It is generally 
due to primary infection, and then involves the cervical lymph- 
nodes secondarily. From there it may by extension gain access 
to the lungs and occasion tuberculosis within them. Secondary 
involvement of the intestines may also occur. 

Syphilis of the tonsils may occur as a primary, secondary, or 
tertiary lesion. 



PHARYNGITIS 177 



PHARYNX 



Circulatory disturbances are usually a part of similar troubles 
of neighboring tissues. 

Inflammation. — The acute catarrhal pharyngitis, or angina, 
may result from exposure to cold, to the irritating action of 
various substances, as tobacco smoke, dust, chemicals, or may 
occur as part of some intestinal derangement. The mucous 
membranes become red and swollen, with, at first, decreased 
secretion. As the process goes on there is frequently an abun- 
dance of a thick tenacious secretion composed of mucus and 
desquamated columnar epithelial cells. In severe cases true 
ulcers may form along the posterior wall. 

In chronic pharyngitis, such as occurs in excessive smokers 
and in those who use their voice a great deal, the posterior 
wall and the faucial pillars are involved particularly. There 
is a chronic congestion and the lymphoid collections become 
hyperplastic, causing slight granular elevations. The secre- 
tions become less, as a rule, but they may be increased in 
amount and mucopurulent in character. The pharyngeal 
tonsils are usually hyperplastic. 

Phlegmonous pharyngitis and retropharyngeal abscess follow 
the entrance of bacteria, usually pyogenic, into the deeper 
tissues, or may result from caries of the spinal column. If the 
abscess formation is rapid, there is bulging into the pharynx 
and rupture may take place. If the process has been slower, 
the pus may extend along the deep fascia until perforation into 
the posterior mediastinum, bronchi, or esophagus occurs. 
General septicemia not infrequently occurs. 

Syphilitic pharyngitis is common as a secondary symptom, 
but it has no characteristic appearance that renders it easily 
recognizable. 

Tuberculous pharyngitis is unusual, but when present is gen- 
erally secondary to tuberculosis of the lungs. 

Pseudomembranous pharyngitis may be diphtheritic or non- 
diphtheritic. 

The non-diphtheritic pharyngitis is generally caused by the 
Streptococcus pyogenes, or may result from the action of very 



178 SPECIAL PATHOLOGY OF THE MOUTH 

irritating substances, such as steam or ammonia. The ap- 
pearance of the pseudomembrane in such cases is, to the naked 
eye, similar to that of the diphtheric variety. It, however, is 
not accompanied by the same constitutional depression, is not 
followed by paralyses, nor is the characteristic bacillus found. 

Diphtheritic pharyngitis is caused by the Klebs-Loffler bacillus 
and is characterized by a pseudomembrane that is yellowish or 
dirty gray in color. The involvement may be limited to a 
small portion of the pharynx, being most common on the 
arches of the fauces, but the tonsils and nares as well may be 
affected. It may extend even into the esophagus and stomach. 

This pseudomembrane is laminated, being composed of fibrin 
in the meshes of which are desquamated epithelial cells, leuko- 
cytes and erythrocytes, and the diphtheria bacilli in great 
numbers. It is formed by the coagulation of the exudate and 
by coagulation necrosis of the superficial tissues. This mem- 
brane can be peeled off, exposing a raw ulcerated surface upon 
which a new membrane quickly forms. The lymph-nodes near 
by may enlarge and undergo suppuration, probably due mainly 
to the presence of pyogenic cocci. 

The extent of the pseudomembrane does not necessarily 
denote the gravity of the infection. The severity depends 
upon the ability of that particular strain of diphtheria bacilli 
to form toxin. The clinical symptoms are the manifestations 
of the intensity of the toxin present. In severe forms the 
membrane may spread rapidly, and if there is a mixed infection 
with streptococci, hemorrhage and even local gangrene may 
result, as well as secondary abscess formation elsewhere in the 
body. Besides the local manifestations there are marked 
general symptoms due to the presence of a dangerous toxin. 
The action of this substance is seen in the form of small foci of 
necrosis in various tissues of the body. Death may result from 
cardiac paralysis due to the action of the toxin. 

Of the internal organs, the liver especially shows focal necrosis 
in which the cells are degenerated, the nuclei showing hyper- 
chromatosis. There is also hyperemia of the kidney, with 
cloudy swelling of the epithelium, edema, and even hemorrhage. 
Inflammation of the heart muscle (myocarditis) and degenera- 



PAROTITIS 179 

tion of the cardiac muscle also occur. The spleen is com- 
monly hyperemic. 

During convalescence, paralysis, particularly of the throat, 
may occur, also of the muscles of the eyes, the larynx, and the 
diaphragm. The muscles will show a round-cell infiltration 
between the fibers, and a granular and fatty change of the 
cells. 

There may be degeneration of the ganglion cells of the cord. 

Vincent's angina is an infection of the pharyngeal mucous 
membrane due to the presence of fusiform bacilli and spiro- 
chetes. The disease differs from an ordinary acute pharyn- 
gitis due to streptococci or staphylococci in that the constitu- 
tional symptoms are less severe and that there is a great tend- 
ency to ulcerations. The submaxillary glands may be swollen. 

Tumors of the pharynx are rare. Squamous epithelioma as 
a result of extension is the most common, but fibroma and 
sarcoma have been observed. 

SALIVARY GLANDS 

Inflammation of the parotid gland, parotitis or mumps, occurs 
as a primary disease, evidently due to some bacterium. The 
infection probably occurs by way of the parotid duct. The 
gland becomes much swollen and tense on account of a marked 
serous exudation. Although abscess formation may seem 
imminent, it is very unusual for suppuration to occur. The 
exudate may be absorbed and the gland very quickly return to 
its normal condition. Sometimes a chronic induration may 
remain or, if abscess formation with rupture has occurred, a 
fistula may result. Secondary involvement of the testicles or 
ovaries may occur either during the attack or shortly after the 
primary inflammation has subsided. The infecting agent is 
evidently in the sputum. 

Suppurative parotitis is not uncommon in the inflammation 
of the parotid gland secondary to infectious diseases, as typhoid, 
scarlet fever, and diphtheria. Small abscesses may form and 
become confluent. The interstitial tissue of the gland is more 
or less infiltrated with pus-cells, and the parenchyma cells may 
undergo fatty degeneration. The inflammation may be con- 



l8o SPECIAL PATHOLOGY OF THE MOUTH 

fined to the gland or it may spread to adjacent parts, some- 
times causing much destruction of tissues. It may give rise 
to inflammation of the brain or of the inner ear, or even to 
metastatic pyemic abscesses in different parts of the body. 
The condition may become chronic, with hyperplasia of the 
fibrous connective tissue, or it may subside and leave no traces. 

Ludwig's angina is a very severe form of inflammation of the 
submaxillary gland. The infection extends into the surround- 
ing tissues with suppuration that may extend beneath the tongue 
and jaw, and to the structures around the larynx and pharynx. 
Sometimes the cellular tissue of the neck may be involved. 
Abscesses may form and discharge either externally or into the 
mouth. Necrosis and gangrene are commonly present and 
death frequently occurs. This condition may follow infection 
by means of carious teeth or involvement of the gland itself 
during the course of an infectious disease, particularly scarlet 
fever. 

Fistulae of the salivary ducts may follow traumatism or the 
perforation of an abscess. The parotid duct is the one gener- 
ally involved. 

Concretions, or calculi, are sometimes found and are called 
sialoliths. They are composed of phosphate and carbonate of 
calcium, and occur in the smaller as well as in the main ducts. 
They frequently give rise to retention cysts, the most common 
variety being that known as ranula, a term applied not only to a 
cystic condition of Nuhn's glands, but of the sublingual as well. 

Tumors of the salivary gland are not uncommon, the parotid 
being the one most frequently involved; the connective- tissue 
tumors, as fibroma, lipoma, chondroma, and sarcoma, being 
the most usual. Adenoma and primary carcinoma are infre- 
quent. The most common neoplasm is the mixed tumor of the 
parotid. This is composed mainly of undeveloped connective 
tissue, but includes cartilage and mucous and fibrous tissues. 
It grows slowly, seldom gives rise to metastasis, and, when 
excised, rarely returns. It is probably the result of inclusions 
taking place in fetal life during the closure of the first branchial 
cleft. Typical endotheliomata, usually of the lymph-vessel type, 
are also encountered. 



CHAPTER XI 

BACTERIA 

These organisms are of interest in that they may be parasitic 
upon and within the body of man, of the lower animals, and 
other plants. The less important ones will be presented first, 
the bacteria being discussed more fully later; these latter 
being especially important on account of their relation to dis- 
ease and their bearing upon general hygiene and preventive 
medicine. 

THE YEASTS 

The yeasts, blastomycetes or saccharomycetes, are unicellular 
fungi which multiply by budding, in which naked asci (spore 
cases) are formed freely on the mycelium. The yeast cell is, 
as a rule, oval, but among the wild yeasts, or torulae, spheric 
forms are common. Great variations occur in size, yeasts 
measuring usually from 10 to 20 f/ in length, with a width of 
about one-half or two-thirds of the long diameter. They 
possess a well-defined, doubly contoured cell-membrane, com- 
posed chiefly of cellulose, and the cytoplasm, unlike that of 
the bacteria, shows definite structure. These organisms 
multiply by budding, at which time the mother-cell sends out 
a small globular projection of the cell membrane into which 
maternal cytoplasm flows. This bud gradually enlarges until 
it becomes about the same size as that of the original cell. 
Finally, by the gradual narrowing of the isthmus connecting 
the two, the daughter-cell becomes complete and free. When 
the surrounding conditions are unfavorable most yeasts are 
able to form spores. These, called "ascospores," are formed 
within the yeast cell itself, each spore forming a separate mem- 
brane of its own, but all of them lying well protected within 
the original cell-membrane. 

In this family Besson includes the following parasitic yeasts: 
the Endomyces albicans (Oidiuni albicans), the parasite of 



162 BACTERIA 

thrush; the Cryptococcus dermatitis {Blastomyces dermatitis), 
the cause of a form of chronic dermatitis; and the Saccharo- 
myces tumefaciens. 

THE MOLDS 

In this group, the hyphomycetes, may be included many 
organisms having in common the formation of a well-marked 
mycelium, but differing so greatly in other respects as to be 
placed in widely separated groups in the systematic arrange- 
ment of the fungi. The characteristic feature of this class is 
the formation of long, interlacing filaments or threads, known 
as mycelia. From these there extend branches called hyphae. 
In this class may be placed the Achorion schonleini (the parasite 
causing favus) , the Trichophyton and Microsporon, the Mucor, 
the Aspergillus, and Eurotium. These parasitic organisms are 
described in detail under the headings of the diseases caused by 
them. 

THE HIGHER BACTERIA 

This group occupies an intermediate position between the 
true bacteria and the molds. These organisms are character- 
ized by filamentous forms with real or apparent branchings. 
The filaments are usually divided transversely, appearing as if 
composed of bacilli. The free ends only seem to be endowed 
with the ability to reproduce, and they develop peculiar ele- 
ments that differentiate the higher from the other bacteria, 
whose cells are all equally free and independent. 

Leptothrix. — These comprise long threads which do not 
branch, and are at times separated with difficulty from chains of 
bacilli. They rarely cause trouble, but have been observed in 
connection with inflammations of the mouth and pharynx, 
particularly along the edges of the tonsillar crypts, where they 
grow with the formation of persistent white patches. Cultiva- 
tion of the leptothrix is difficult. 

Cladothrix is a thread-like form in which false branching 
may be recognized, an appearance resulting from the frag- 
mentation of the threads. The terminal cell breaks away from 
the main stem, is set at an angle by the elongation of the thread 
itself, and, as both continue to divide, the simulation of true 



CLASSIFICATION OF THE BACTERIA 1 83 

branching is produced. This type is probably not pathogenic; 
most of the cases ascribed to this class were likely due to strepto- 
thrix infection. 

Streptothrix denotes forms with numerous true branches and 
spores which usually appear in chains. Xumerous cases of 
disease have been reported as being caused by these organisms. 

Actinomyces is characterized by the formation of club-shaped 
ends and the radiating arrangement of the threads. This 
organism causes a specific disease of the lower animals, some- 
times transmitted to the human being. 

BACTERIA 

Bacteria are minute unicellular organisms, probably belong- 
ing to the vegetable kingdom, the schizomycetes. It is difficult 
to classify them, but probably the best arrangement is a modi- 
fication of Migula's method as follows: 

CLASSIFICATION OF THE BACTERIA 

I. ORDER: EUBACTERIA (True Bacteria) 

A. Sub-order: Haplobacteria (Lower Bacteria) 

I. Family Coccace^e. Cells globular, becoming slightly elongate before 
division. Division in one, two, or three directions of space. Forma- 
tion of endospores very rare. 

(A) Without nagella. 

1. Streptococcus. Division in one direction of space, producing 

chains like strings of beads. 

2. Micrococcus. Division in two directions of space, so that tetrads 

are often formed. 

3. Sarcina. Division in three directions of space, leading to the 

formation of bale-like packages. 

(B) With nagella. 

1. Planococcus. Division in two directions of space, like micro- 

coccus. 

2. Planosarcina. Division in three directions, like sarcina. 

II. Family Bacteriace.e. Cells more or less elongate, cylindric, and 
straight. They never form spiral windings. Division in one di- 
rection of space only, transverse to the long axis of the cell. 

(A) Without nagella. 

1. Bacterium. Occasional endospores. 

(B) With nagella. 

2. Bacillus. Flagella arising from any part of the surface. Endo- 

spore formation common. 

3. Pseudomonas. Flagella attached only at the ends of the cell. 

Endospores very rare. 



184 BACTERIA 

III. Family Spirillace^e. Cells twisted spirally like a corkscrew, or 

representing sections of the spiral. Division only transverse 
to the long diameter. 

1. Spirosoma. Rigid; without flagella. 

2. Microspira. Rigid; having one, two, or three undulating flagella 

at the ends. 

3. Spirillum. Rigid; having from five to twenty curved or un- 

dulating flagella at the ends. 

4. S pirochceta. 1 Serpentine and flexible. Flagella not observed; 

probably swim by means of an undulating membrane. 

B. Sub-order: Trichobacteria (Higher Bacteria) 

IV. Family Mycobacteriace^e. Cells forming long or short cylindric 

filaments, often clavate-cuneate or irregular in form, and at 
times showing true or false branchings. No endospores, but 
formation of gonidia-like bodies due to segmentation of the cells. 
No flagella. Division at right angles to the axis of rod in fila- 
ment. Filaments not surrounded by a sheath as in Chlamydo- 
bacteriaceae. 

1. Myobacterium. Cells in their ordinary form, short cylindric 

rods often bent and irregularly cuneate. At times Y-shaped 
forms or longer filaments with true branchings may produce 
short coccoid elements, perhaps gonidia. (This genus includes 
the Corynebacterium of Lehmann-Neumann.) No flagella. 

2. Actinomyces. Cells in their ordinary form as long branched 

filaments; growth coherent, dry, or crumpled. Produce gonidia- 
like bodies. Cultures generally have a moldy appearance, due 
to the development of aerial hyphae. No flagella. 
V. Family Chlamydobacteriace^. Forms that vary in different 
stages of their development, but all characterized by a surround- 
ing sheath about both branched and unbranched threads. Divi- 
sion transverse to the length of the filaments. 

1. Cladothrix. Characterized by pseudodichotomous branchings. 

Division only transverse. Multiplication by the separation of 
whole branches. Transplantation by means of polar flagellated 
swarm-spores. 

2. Crenothrix. Cells united to form unbranched threads which 

in the beginning divide transversely. Later the cells divide 
in all three directions of space. The products of final division 
become spheric, and serve as reproductive elements. 

3. Phragmidiothrix. Cells at first united into unbranched threads. 

Divide in three directions of space. Late in the development, 
by the growth of certain of the cells through the delicate, 
closely approximated sheath, branched forms are produced. 

4. Thiothrix. Unbranched cells inclosed in a delicate sheath. 

Non-motile. Division in one direction of space. Cells contain 
sulphur grains. 

1 The spirochseta and some closely related forms are now thought to 
be more properly classified among the protozoa than among the bacteria. 



MOTILITY 



II. ORDER: THIOBACTERIA (Sulphur Bacteria) 

I. Family Beggiatoace^e. Cells united to form threads which are 
not surrounded by an inclosing sheath. The septa are scarcely 
visible. Divide in one direction of space only. Motility accom- 
plished through the presence of an undulating membrane. Cells 
contain sulphur grains. 
There are two families, numerous subfamilies, and thirteen genera in 
this order. They are all micro-organisms of the water and soil, and 
have no interest for the medical student. 



A more common, but less accurate method of classification 
divides bacteria into: 

i. Bacillus. — A rod-shaped organism that is not curved or 
twisted upon itself, one diameter being distinctly greater 
than the other. 

2. Micrococcus or Coccus. — A minute spheric organism. 

(a) Diplococcus, when occurring in twos. 

(b) Streptococcus, when occurring in chains. 

(c) Staphylococcus, when in bunches like grapes. 

(d) Tetracocci, when division takes place in two directions, 
and the individuals remain attached in groups of four. 

(e) Sarcina, when dividing in three directions, giving rise 
to bale-like packages. 

(/) Zooglea, when grouped in irregular masses. 

3. (a) Spirillum. — An organism twisted like a corkscrew 
and rigid; usually has polar flagellar 

(b) Spirochceta, when the organism is long, slender, flexible, 
and without rlagella. 

(c) Vibrio. — A short organism, bent like a comma, usually 
with a single end-nagellum. 

Structure. — Bacteria are composed of a small amount of 
cytoplasm surrounding a large but indistinctly defined nucleus. 
In this cytoplasm may be found granules of fat, pigment, 
sulphur, etc. Each cell is surrounded by a distinct cell-wall, 
and sometimes there is present a peculiar gelatinous material 
forming a capsule. 

Motility. — The greater number of bacteria are non-motile, 
but many possess the power of motility as a result of the presence 
of rlagella. Most of the cocci are non-motile. According to 



i86 



BACTERIA 




Fig. 77. — Types of Micro-organisms. 

1, Coccus; 2, streptococcus; 3, staphylococcus; 4, capsulated dip- 
lococcus; 5, biscuit-shaped coccus; 6, tetrads; 7, sarcina form; 8, types 
of bacilli (1 to 8 are diagrammatic); 9, non-septate spirillum (X 1000); 10, 
ordinary spirillum: (a) comma-shaped element; (b) formation of spiral by 
comma-shaped elements (X 1000); 11, types of spore formation; 12, 
flagellated bacteria; 13, changes in bacteria produced by plasmolysis 
(after Fischer); 14, bacilli with terminal protoplasm (Biitschli); 15, (a) 
Bacillus composed of five protoplasmic meshes; (b) protoplasmic network 
in micrococcus (Biitschli); 16, bacteria containing metachromatic granules 
(Ernst Neisser); 17, Beggiatoa alba — both filaments contain sulphur gran- 
ules — one is septate; 18, Thiothrix tenuis ( Winogradski) ; 19, Leptothrix 
innominata (Miller); 20, Cladothrix dichotoma (Zopf); 21, Strep tothrix 
actinomyces (Bostrom) : (a) colony under low power; (b) filament showing 
true branching; (c) filament containing coccus-like bodies; (d) filament with 
club at end. 



the presence or absence of flagella, the following classification 
of bacteria has been made: 



REPRODUCTION 187 

i. Gymnobaderia, forms without flagella. 
2. Trichobacteria, forms with flagella. 

(a) Monotricha, a single flagellum at one end. 

(b) Leptotricha, a bundle of flagella at one end. 

(c) Amphitricha, a flagellum at each end. 

(d) Peritricha, flagella arising from all parts of the surface 
of the organism. 

Size. — Bacteria are so minute that a special unit has been 
adopted for their measurement. This is the micromillimeter 
(ft), or one- thousandth part of a millimeter, known as the 
micron. It is equivalent to the one-twenty-five-thousandth 
part of an inch. The size of bacteria vary from a fraction 
of a micromillimeter to 20 or even 40 micromillimeters. 

Reproduction. — Fission. — The most common method in 
which the organisms divide into two. This occurs very 
rapidly if there is enough nutritive material present and the 
surrounding conditions are- favorable, the length of a genera- 
tion varying from fifteen to forty minutes. 

Sporulation occurs when the conditions do not favor multi- 
plication. There are then formed small, round or oval, highly 
refracting bodies called spores, which are capable of resisting 
very unfavorable surroundings. They differ from bacteria in 
being able to withstand evaporation and exposure to quite 
high degrees of heat. Few adult bacteria can resist tempera- 
tures above 70 C, but spores are uninjured by such heat and 
may even resist the temperature of boiling water (ioo°- C.) for 
a short time. If the spore develops within the bacterium in 
the middle, or at one or other of the ends, it is called an endo- 
spore. If the spore is so large as to cause a bulging of the organ- 
ism it is called a Clostridium. These forms occur in the bacilli. 
Among the micrococci there are times when the entire organ- 
ism is transformed into a spore, an arthrospore. 

Germination of Spores. — When conditions become favorable 
the spore may develop into an adult organism. Its contents, 
which have been clear and transparent, become granular, the 
body increases slightly in size, the capsule becomes less dis- 
tinct, and in the course of time splits open to allow the escape 
of the young organism. This begins to increase in size, develops 



I 88 BACTERIA 

its characteristic capsule, and presently begins to multiply by 
fission. 

Growth of Bacteria. — In the cultivation of bacteria there are 
many conditions that can influence the growth favorably or 
unfavorably. There are, however, certain factors that are 
really essential. 

Food. — Bacteria grow best when diffusible albumins are 
present, but carbohydrates will do. It has been found that the 
food requirements differ very greatly with the different kinds 
of organisms. Some will live in water to which an extremely 
small amount of organic matter has been added. Others re- 
quire a concentrated medium such as blood-serum. Then, too, 
the addition of certain substances, such as glucose or glycerin, 
may exert a very favorable influence. 

Oxygen. — All micro-organisms must have oxygen in order to 
continue to live, but it may be present either in the free or in a 
combined condition. Those organisms which grow in the pres- 
ence of free (uncombined) oxygen are known as aerobes. Those 
which will not grow in the presence of free oxygen are the 
anaerobes. There are, however, some of the aerobic type which 
will grow about as well without free oxygen as with it; these are 
the optional (facultative) anaerobes. 

Moisture to some degree is an absolute necessity, but it may 
be . present in very slight amount. Unless some is present 
nearly all organisms will dry up and cease to multiply, but 
spores may be formed first and persist more or less indefinitely. 
In making up artificial culture-media there should be present 
at least 80 per cent, of water. 

Temperature of a proper degree is of the greatest importance. 
Every micro-organism grows best at some, definite degree of 
heat, and shows variations in its activity as the temperature 
changes. The organisms, however, may be able to endure 
extreme degrees of cold without being destroyed — some can 
be placed in liquid air and yet undergo multiplication when 
the temperature is raised. They cannot, as a rule, stand the 
higher temperatures as well, although a few varieties of organ- 
isms may thrive at high degrees (65°-7o° C). They are called 
thermophilic, and are found in manure piles and hot springs. 



GROWTH OF BACTERIA 1 89 

The temperature at which micro-organisms grow best is known 
as the optimum; the lowest temperature at which they continue 
to multiply, as the minimum; the highest at which they remain 
active, the maximum. With pathogenic or disease-producing 
organisms the optimum temperature is that normal to the body 

(37° C). 

A temperature of from 50 to 6o° C. will weaken and finally 
destroy nearly all forms. If they are exposed to steam or boil- 
ing water at the temperature of ioo° C. all fully developed 
bacteria will be killed in a few minutes, but their spores 
may be able to resist this heat for a longer time. When dry 
heat is used a higher temperature is required. The spores 
may withstand 15c C. for an hour or 175 C. for five to ten 
minutes. 

Reaction. — Most true bacteria grow best in neutral or feebly 
alkaline media, although some grow well in strong acids and 
others in marked alkalinity. 

Many chemical bodies will restrain the growth or destroy 
the bacteria. These substances may be produced by the 
bacteria in their growth or they may be artificially introduced. 
Those which will restrain the growth but not kill are called 
antiseptics; those that kill, germicides. 

Light, particularly the direct rays of the sun, will retard 
bacterial growth and in many cases kill the organisms. Certain 
colors distinctly retard growth, blue being the most effective. 
A weak, diffused light seems most favorable, but various organ- 
isms react differently, certain bacteria producing color only 
when exposed to the ordinary light of a room, while others 
will produce color only in the dark. 

Motion. — Bacteria apparently grow best when there is an 
absence of motion. 

Electricity and x-rays do not seem to have any constant effect 
upon bacteria. 

Symbiosis, or the association of one organism with another, 
may cause an increase in its activity, as the growth of the tetanus 
bacillus in the presence of other bacteria that use up the supply 
of oxygen. Antibiosis is the condition in which the associa- 
tion may be detrimental to one of the organisms. 



190 BACTERIA 

Products of Bacterial Growth. — According to the substances 
formed as a result of their growth bacteria may be divided 
into: 

Zymogens, bacteria of fermentation. 

Saprogens, bacteria of putrefaction. 

Chromogens, bacteria which produce colors. 

Photogens, phosphorescent bacteria. 

Aerogens, gas producers. 

Pathogens, bacteria which produce disease. 

Bacteria through their activity split up complex organic sub- 
stances into simple compounds. 

Fermentation is the splitting up of carbohydrates by the 
activity of the micro-organisms. This is the process that takes 
place in the formation of alcohol as a result of the action of 
yeast. Other forms of fermentation are those in which acetic, 
lactic, or butyric acids result. 

Putrefaction is the breaking up of nitrogenous compounds by 
micro-organisms that can live only in dead organic substances. 
The albumins are first transformed into peptones, which split 
up into gases, acids, bases, and salts. 

The albumins may become changed to toxalbumins or into 
alkaloidal substances called ptomains, which are "chemical com- 
pounds, basic in character, formed by the action of bacteria 
upon organic matter." Ptomains are generally formed outside 
of the living body and cause harm only when introduced within 
it. 

Toxins and toxalbumins are poisonous substances elaborated 
by bacteria during growth, and it is upon them that the disease- 
producing power of the organism rests. 

The bacterio proteins also belong to this same group. These 
bacterial products are destroyed by sunlight, by heating to 
6o° to 8o° C, by long keeping, and by the gastric juices. Tuber- 
culin is an exception, in that it remains unaltered at a tempera- 
ture of ioo° C. The poisonous bodies may be either soluble or 
insoluble, and are generally peculiar to the variety of organism 
by which they are formed. Certain ones select definite cells 
upon which they act, and are called specific. Others, having 
no special selective powers, are non-specific. 



PRODUCTS OF BACTERIAL GROWTH 191 

Chr ontogenesis. — Bacteria that produce colored colonies or 
give a color to the medium in which they grow are called 
chromogenic; those producing white or no color, non-chr onto genie. 
Most chromogenic organisms are saprophytic and non-patho- 
genic; but some of the pathogenic forms may produce color. 
Almost all known colors may be formed by different bacteria, 
and sometimes one organism will form two or more colors. 
The formation of the pigment probably depends upon the 
presence of oxygen. 

Acrogenesis. — During fermentation and decomposition various 
gases are given off, such as carbon dioxid, sulphureted hydrogen, 
ammonia, etc. 

Other enzymes formed by bacteria may cause the coagula- 
tion of milk and the liquefaction of gelatin. Some bacteria 
liquefy the gelatin in such a peculiar and characteristic manner 
as to make the appearance a valuable guide for the differentia- 
tion of species. 

Pathogenesis. — Those micro-organisms which cause disease 
are called pathogenic; those that do not, non- pathogenic. There 
is, however, no sharp line between the two, as under adverse 
cultural conditions the pathogens may lose their ability to pro- 
duce disease. On the other hand, those that are usually harm- 
less may be made virulent. 



CHAPTER XII 

STERILIZATION AND DISINFECTION 

In all bacteriologic work the underlying factor of success 
is that no organisms, other than those with which we are work- 
ing, should gain entrance into the utensils or materials used, 
or that they should be destroyed if present. Inasmuch as 
bacteria are always present in the dust, we must be constantly 
on guard. If no living matter is present in any of the articles 
used, they are said to be sterile. 

By sterilization is meant the destruction or removal of all 
forms of micro-organisms. Disinfection refers to the destruc- 
tion of the infectious organisms alone. A germicide is any sub- 
stance that will kill germs. An antiseptic is a substance that 
will prevent the growth of micro-organisms, but will not neces- 
sarily kill them. 

The table on page 193, from McFarland, gives in brief the 
various ways by which different materials may be sterilized. 

It should be remembered that a higher temperature is re- 
quired when dry heat is used than when there is moisture 
present. Although most adult bacteria are killed by a tem- 
perature of 6o° C, the spores may resist ioo° C. as long as an 
hour. Consequently, a much higher temperature must be em- 
ployed in order that all forms may be destroyed. The platinum 
wires used for the inoculation of culture-tubes are sterilized 
by being held in the direct flame until incandescent. Care 
should be taken to sterilize the handle, lest micro-organisms 
from it might contaminate the cultures. 

After the culture-tubes have been cleaned and dried, they 
are stoppered with plugs of non-absorbent cotton and then 
placed in the hot-air sterilizer. Although the tubes are steril- 
ized the real purpose is to so mold the plugs that when removed 
from the tubes they will retain their shape. 
192 



STERILIZATION 193 










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o 



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Q 3 jr'" 1 f <t 




18 III I I 

3 S a-*?? ~-' _, ^>°pc-v<3 S2cr C p 

h*,£. o _^ CL ^ p 3 !^ SSS- P « 

sg-siisg*. k|o |.s| 1 ^ 



13 



194 



STERILIZATION AND DISINFECTION 



Sterilization of Culture-media. — For this purpose dry heat 
cannot be used, as it would cause the water, some 80 per cent., 
to evaporate and the media would be dry and useless. Conse- 
quently, steam must be employed, but as the temperature of 
ioo° C. does not kill the spores, it is necessary that the media 
be exposed more than once. The method employed is known as 
intermittent sterilization; the apparatus used is the Arnold 
sterilizer. In this method the materials to be sterilized are 




Fig. 78. — Arnold's Steam Sterilizer (Boston Board of Health form). 

exposed to steam for fifteen to thirty minutes; they are then 
allowed to cool and stand for twenty-four hours. At the end 
of this time the heating is repeated, and after another interval 
of twenty-four hours they are exposed once more to the steam. 
Those spores that may have survived the first heating will have 
had time to develop into adult organisms and will be destroyed 
the second time. The third heating is largely a matter of pre- 
caution. 



DISINFECTION IN GENERAL 



195 



Another method of sterilization is that known as pasteuriza- 
tion. In this the substances to be sterilized are exposed to a 
temperature of from 6o° to 70 C. for about one hour. This 
form, however, is not suitable if the organisms are spore formers. 
It is commonly employed in the commercial handling of milk. 

When time is an important ele- 
ment, and the media used can resist 
high temperature, sterilization by 
means of the autoclave is most satis- 
factory. This instrument is a metal 
cylinder with a top that can be 
screwed down tight. Into this is 
placed about 1 liter of water, the 
culture-media is placed on shelves, 
the lid closed, and a Bunsen burner 
placed beneath. In this way, as 
the steam is under pressure, a tem- 
perature of no° C. is soon obtained. 
Exposure to this for about one-half 
hour will destroy all spores as well 
as adult bacteria. 

When the sterilization is com- 
pleted, if "slant" cultures are to be 
made, the test-tubes are so placed 
that the medium will come about 
half-way up the side of the tube. 
When the media have solidified, the 
tubes can be kept in a moist con- 
dition for a longer period if the 
excess of the cotton plugs is trimmed 
off and rubber caps be put over the 
ends. 

Some liquids may be sterilized by being passed through 
special filters, those having openings so minute that the fluid 
can pass through, but not the micro-organisms. 

Disinfection in General. — There are many solutions of 
various substances that are used for disinfecting, but it is neces- 
sary to understand the limitations of many of these substances 




Fig. 79. — Modern 

CLAVE. 



Auto- 



196 STERILIZATION AND DISINFECTION 

in order to obtain proper results. Bichlorid of mercury (mercuric 
chlorid) is the most popular of the germicides for general use, 
as it is active, soluble, and cheap. It has, however, certain 
very marked disadvantages, it is very poisonous, is destructive 
to metal instruments, and is readily converted into a harmless 
compound if it comes in contact with albuminous matters. 
This latter fault may be corrected by adding to the mercuric 
solution a weak acid — as tartaric. Most of the mercuric 
tablets as purchased are combined with some acid. For ap- 
plication to the skin solutions of from 1 : 1000 to 1 : 2000 should 
be used; for large wounds and cavities, 1: 10,000 to 1: 5000; for 
small wounds, 1 : 2000. 

Carbolic acid is not as reliable as mercuric chlorid, but it 
quickly destroys pus-organisms. It is readily soluble, is not 
affected by albuminous compounds, and does not injure metal 
instruments. It is quite poisonous and causes a local numbing 
of the tissues with which it comes in contact. It is used in a 
solution of 1 : 20 for cleansing suppurating wounds, sinuses, and 
abscess cavities. Peroxid of hydrogen acts through its ability 
to give off oxygen when brought in contact with organic matter. 
It is valuable as a mouth- wash where it can come in contact with 
the superficial tissues. Can be used in solutions of 50 per cent, 
or less. Formaldehyd in the form of a 40 per cent, solution 
in water, known as "formalin," is one of the most useful of all 
germicides. It is, however, too irritating to the skin and 
mucous membranes for general surgical use; its chief value is 
as a disinfectant. Although very diffusible, formaldehyd has 
very little penetrating power, and consequently can be con- 
sidered only as a surface disinfectant. For this purpose it has 
marked advantages in that, although a powerful germicide, 
it is comparatively harmless to higher animals, and also has no 
injurious effect upon cloths or metals. The best method to 
employ is to mix powdered permanganate of potassium with 
an equal amount of sand, and to this add formalin. The for- 
maldehyd gas will be given off freely, but there will be no 
danger of an explosion, as may occur if the sand is omitted. 
The room to be disinfected must, of course, be carefully sealed, 
with the exception of one door, which should be sealed as soon 



DISINFECTION OF CLOTHING 1 97 

as the formalin has been added. About i quart of formalin 
should be evaporated for every iooo cubic feet of room space. 
Sheets wet with formalin may be hung up in the room as a 
make-shift substitute for the above. 

Disinfection of the hands is of the greatest importance when 
dealing with patients, in order to avoid all possibility of trans- 
mitting any disease from one person to another. Ordinary 
washing with soap and water, although sufficient as a rule, 
does not get the skin free from bacteria. Probably the most 
satisfactory method is to wash the hands for ten minutes in as 
hot water as can be comfortably borne, using a sterilized stiff 
nail-brush with plenty of soap, then rinse off the soap in clean 
hot water. 

All instruments should be washed and then sterilized by 
being boiled for ten to fifteen minutes in water containing a 
small amount (i to 2 per cent.) of soda (carbonate, bicarbonate, 
or biborate), in order to prevent rusting. Great care should be 
taken to have all instruments clean, lest infection should be 
carried from one person to another. Syphilis has been conveyed 
by unclean dental instruments. 

Disinfection of Dejecta. — When possible, all discharges should 
be destroyed by fire, but this method is limited practically to 
expectorations and nasal discharges. In diphtheria or in other 
infectious conditions of the mouth, throat, and nose the dis- 
charges should be received in old cloths, paper napkins or paper 
boxes, and then burnt. The intestinal discharges in typhoid 
fever should be intimately mixed with a 5 per cent, solution of 
chlorinated lime, and be allowed to stand for one hour before 
being disposed of. 

Disinfection of Clothing. — All fabrics coming in contact with 
a case of infectious disease must be considered as dangerous 
until they have been sterilized properly. Such materials can 
be placed in the wash-boiler and boiled for one-half hour, then 
hung up out-of-doors to dry exposed to the sun. Outer clothes 
cannot be treated in such a manner, and should be exposed to 
hot air at a temperature of no° C. This is difficult, as no 
arrangements exist in private houses for carrying out this 



198 STERILIZATION AND DISINFECTION 

method. About the most that can be done is to expose them 
for some hours to fresh air and sunlight. 

Disinfection of Furniture, Etc. — In addition to the disinfec- 
tion of the room with formaldehyd, the floor should be scrubbed 
(using rubber gloves) with formalin, 5 per cent, carbolic acid 
solution, or 1: 1000 mercuric chlorid solution (no soap should be 
used with the latter, as it combines with the chlorid solution 
and prevents its action). 



CHAPTER XIII 
BACTERIOLOGIC METHODS 

CULTURE-MEDIA 

As has already been stated (p. 21), there are certain require- 
ments known as Koch's laws, or postulates, that must be ful- 
filled in order that we can prove a certain organism to be the 
cause of a definite pathologic condition. These require, among 
other things, that the organism be grown outside of the body 
on artificial culture-media; these to be composed of such 
substances in such proportion as will enable the bacteria to 
live and multiply. Inasmuch as the different bacteria vary 
greatly in their metabolic activities, it becomes necessary to 
have various kinds of media; there are, however, certain forms 
that are employed routinely. Such media should contain at 
least 80 per cent, of water, should be of neutral or feebly alkaline 
reaction, and of a composition which, for the pathogenic types 
at least, should closely approximate the juices of the animal 
body. Such nutritive materials may be either liquid or solid, 
and some of the most useful may be liquefied and solidified at 
will. 

Bouillon. — This medium is used by itself and also as the 
nutritive basis of certain solid media. It may be made up 
with lean beef or with 3 gm. of beef extract. If the former is 
used it must be freed from fat and gristle and finely minced; 
500 gm. of it are mixed with 1000 c.c. of water and allowed to 
stand on ice for twelve hours. At the end of this time the 
liquor is poured off, that remaining in the meat squeezed 
through a cloth, and enough water added to bring the amount 
up to 1000 c.c. It is then filtered, and to the clear filtrate is 
added 10 gm. of Witte's peptone, 5 gm. of sodium chlorid, and 

199 



200 BACTERIOLOGIC METHODS 

enough water to bring the quantity up to iooo c.c. This mix- 
ture is boiled until everything is dissolved, and it is then neu- 
tralized, as its reaction is very acid. 

The neutralization should be very carefully carried out so 
that the final reaction is slightly alkaline. This is done by care- 
fully adding a 10 per cent, solution of caustic soda and testing 
with litmus-paper. During this process the solution is kept 
boiling. After the materials are all dissolved and the solu- 
tion titrated, it should be allowed to cool before filtering. If 
filtered while hot there will be a subsequent precipitation of 
meat-salts, which will cloud it. 

Glucose bouillon is similar to the above, except that it contains 
i per cent, glucose in addition. 

Agar-agar. — To iooo c.c. of beef bouillon 15 gm. of agar-agar 
are added and boiled for one hour, constantly stirring. Water 
is added at various intervals to keep up the required volume. 
After the boiling is done the contents are allowed to cool to 
6o° C, at which point an egg is beaten into the fluid, which is 
again boiled for about ten minutes. Then filter while hot 
through wet filter-paper. A jacketed filter kept warm by a gas 
flame facilitates the process. As the fluid cools while filtering, 
it has to be again heated until all passes through. The finished 
agar should be a colorless, nearly transparent, firm jelly. 

The purpose of the agar-agar is to give a medium that will 
remain solid at a temperature equal to that of the body, which 
is the best for many bacteria, the agar itself not contributing 
any nourishment to the medium. The agar will melt at about 
42 ° C, but will again solidify when cooled. . 

Gelatin. — To iooo c.c. of boiling beef bouillon add 100 gm. 
of golden seal French gelatin. When the gelatin is thoroughly 
dissolved boil for about five minutes and neutralize by the 
method described for bouillon. The mixture is cooled to 6o° C, 
an egg beaten in, boiled about ten minutes, and filtered through 
wet filter-paper. Sufficient water should be added to bring the 
quantity up to the original amount. It may have to be re- 
heated a couple of times before filtration is complete. As the 
gelatin solution is strongly acid in reaction, it must be corrected 
carefully by titration. Care must be taken not to bring the 



CULTURE-MEDIA 201 

mixture to the boiling temperature more frequently than is 
necessary, as the power of coagulation may be destroyed. 

This medium melts at temperatures above 2 2° C. 

Glucose gelatin is gelatin that has been dissolved in glucose 
bouillon. 

Blood-serum (Loffler' s Mixture). — The blood-serum is ob- 
tained by collecting it at a slaughter-house. Jars holding about 
1 gallon should be used. These should be clean and sterile. 
The collected blood is put aside in a cool place for twenty-four 
to forty-eight hours until the blood is completely clotted. If 
the clot adheres to the side of the jar, loosen it with a glass rod. 
The clear serum is removed with a pipet. This is then mixed 
with glucose bouillon. 

Glucose bouillon (1 per cent.) 1 part 

Beef blood-serum 3 parts 

The above is then run into test-tubes to a depth of about 
4 cm. These are placed on an incline so that they will be on a 
slant when coagulated. In this position they are placed in a 
hot-air sterilizer and kept at a temperature between 85 ° and 
90 C. for one hour. The thermostat should be carefully 
watched so as not to have the heat vary from the above figures. 
After the medium has become thoroughly coagulated the 
tubes are sterilized in steam for one-half hour on three suc- 
cessive days. When blood-serum tubes are not available a 
good substitute in the form of a hard-boiled egg may be used. 
Remove the egg from the water, and with a sterile instrument 
remove a part of the shell, leaving the coagulated albumen 
exposed. Inoculate this surface with the suspected material, 
cover with a glass, and then place near a stove or in a 'Ther- 
mos" bottle, and allow to incubate for eighteen to twenty-four 
hours. The blood-serum is particularly useful in the cultiva- 
tion of the Bacillus diphtheriae, which grows upon it rapidly 
and with a characteristic appearance. 

Litmus Milk. — To milk that has been freed from cream 
enough of a freshly prepared aqueous solution of litmus is 
added to give it a blue color. This is run into test-tubes which 
are treated by intermittent steam sterilization. Fresh milk 



202 BACTERIOLOGIC METHODS 

should be used and the process quickly carried out to prevent 
as much as possible the growth of bacteria. This medium is 
the best for determining the formation of acids or alkalis by 
bacteria. 

Potato Cultures. — The potatoes should be thoroughly 
scrubbed with brush and water. Solid cylinders of a size to 
fit the test-tubes are cut with a cork-borer. They are then 
split obliquely and the pieces placed in running water for some 
twelve hours. The oblique pieces are then placed in test- 
tubes with the larger end downward. A few drops of water 
should be added to prevent drying. The tubes are then put 
through the fractional steam sterilization. 

Dunham's Pepton Solution. — 

Pepton 10 gm. 

Sodium chlorid 5 " 

Distilled water 1000 c.c. 

The pepton and sodium chlorid are dissolved by boiling 
and the mixture filtered. Test-tubes are filled and sterilized. 
This solution is commonly employed for the detection of indol. 

Filling of Test-tubes. — New test-tubes are best cleaned by 
washing in a very weak solution of nitric acid, then rinsing in 
water, and allowing to become dry or nearly so. Old tubes 
that have contained cultures are boiled for nearly one hour 
in a 6 per cent, solution of common soda. 

The cleaned tubes are plugged with raw cotton and placed 
in the hot-air sterilizer at 150 C. until the cotton has turned 
brownish. This is to mold the stopper to the shape of the 
tube. 

To fill the tubes it is best to take a large funnel and by means 
of a short piece of rubber connect it to a piece of glass tubing 
a couple of inches in length. The supply of the medium is 
controlled by a pinch-cock on the rubber. The glass tube 
is inserted into the test-tube, the required amount of medium 
run in, and the cotton plug put back. Care should be taken 
not to get any of the culture-medium on the neck of the tube, 
as the cotton would stick to it. If "slant" cultures are to be 
made, run in about 5 c.c. of fluid; if "stab" cultures, about 8 to 



VARIETIES OF CULTURES 203 

10 ex. should be used. The filled tubes are then sterilized. 
After the final sterilization, if "slant" cultures are to be made, 
the test-tubes are so placed that the medium will come about 
half-way up the side of the tube. 

Instead of test-tubes, flasks of varying sizes may be used to 
contain the medium. 

Varieties of Cultures. — 

1. Slant. 

2. Stab. 

3. Petri dish. 

4. Esmarch tube. 

5. Hanging drop. 

6. Anaerobic. 

1. Slant Cultures. — A platinum wire is taken and heated 
in the flame. When cool it is inserted into the material to be 
examined. Then, without touching anything, not even the 
sides of the tube, the point of the wire is carefully drawn over 
the surface of the medium and the wire again sterilized. When 
the cotton plug is removed, the end of the tube should be 
passed through the flame. Care should be taken at all times 
that the platinum wire is carefully sterilized before being laid 
anywhere. 

2. Stab cultures are made by carefully inserting the platinum 
wire, which should be straight, into the center of the culture- 
media. The same precautions as mentioned above should 
be observed. 

3. The Petri dish consists of a shallow glass dish with a 
cover. It is used to a large extent for the purpose of isolating 
colonies and obtaining pure growths. The tubes inoculated 
directly from the material examined usually contain several 
varieties of organisms. The method of isolating is as follows: 
Three tubes of agar-agar or gelatin are melted and then placed 
in a water-bath at a temperature between 40 and 42 ° C. A 
platinum wire with a small loop at the end is inserted into the 
infected substance and then a tube is inoculated. From this 
tube a loopful is carried over to tube No. 2, and a third tube 
is inoculated from the second, the platinum wire being sterilized 
each time. Three sterile Petri dishes are taken and a tube 



204 BACTERIOLOGIC METHODS 

is inserted under the cover of one and its contents poured out. 
This is done with all three, care being taken to have the medium 
evenly distributed over the bottom of the dish. They are then 
incubated twenty-four hours at a temperature of 37 C. 

The first tube will contain so many organisms that Petri 
dish No. 1 will be covered with colonies. The second tube, 
being diluted, will give fewer colonies on dish No. 2, while dish 
No. 3, obtained by pouring out tube No. 3, will have only a few 
scattered colonies. From this last dish the individual growths 
may be removed with a sterilized platinum needle and in- 
oculated into a fresh tube, a pure culture thus being obtained. 

4. The Esmarch tube is made by taking an inoculated tube 
of melted agar or gelatin, laying it on a block of ice, and rotating 
till the medium is distributed in a thin coat on the inside. 
Care must be taken that the contents do not come in contact 
with the cotton plug. This method has been practically sup- 
planted by the Petri dishes. 

5. Hanging-drop cultures are obtained by taking a slide 
in which there is a depression and a ring of vaselin is made 
around it. A sterilized cover-glass is taken, a drop of bouillon 
placed on it, and this is inoculated with the usual precautions. 
The cover-glass is inverted over the depression in the slide and 
pressed down upon the vaselin. This is put in the incubator for 
twelve to twenty-four hours and then examined. 

6. Anaerobic cultures may be obtained in various ways, the 
essential point being the elimination of free oxygen. A test- 
tube half full of a medium that will become solid on cooling 
is boiled, rapidly cooled, and then inoculated by a deep stab. 
On top of this may be poured melted paraffin, oil, or vaselin to 
keep out the air. Buchner's method consists in the use of two 
tubes, a small one to contain the culture, and a larger one to 
contain a fluid that will absorb the atmospheric oxygen. The 
solution used consists of pyrogallic acid and sodium hydroxid, 
about 2 gm. of the former, 20 c.cm. of a 10 per cent, solution of 
the latter. This is poured into the larger tube, the smaller one 
placed within it, and it is then tightly corked. A simpler 
method is one in which a larger tube containing a liquid medium 
is used. Into this is placed a smaller tube with the closed end 



STAINING BACTERIA 



20: 



uppermost. During sterilization the air will be displaced, and 
when the liquid cools the smaller tube will be full of the medium. 
In this the anaerobic organisms will grow. This method is 
also of value in determining whether there is any gas formation, 
and may be used in place of Smith's fermentation tubes. 

The oxygen within the container may be replaced by an 
atmosphere of hydrogen, and the latter tightly sealed. 



EXAMINING BACTERIA 

Although the greater part of the examination of micro- 
organisms is done with stained specimens, yet they should 
always be examined in the unstained and living condition as 
well. The best way to do this is by means of the hanging drop. 




Fig. 80. — The " Hanging Drop " seen prom Above and in Profile 

(McFarland). 

In this method a slide with a concavity is used. Around this de- 
pression a ring of vaselin is made. A drop of the material to be 
examined is placed in the center of a clean cover-glass, which is 
then inverted over the depression in the slide and is pressed 
down upon the vaselin. Care should be taken that the drop 
is not large enough to touch the slide. The edge of the drop 
should be examined, as the central portion is too thick. By 
this method can be determined the shape, size, grouping, divi- 
sion, sporulation, and motility of the organism. 

STAINING BACTERIA 

Staining Cover-glass Preparations. — A well-cleaned cover- 
glass or slide has a small portion of the material for examina- 



206 BACTERIOLOGIC METHODS 

tion spread out on it in a very thin layer by means of a sterilized 
platinum wire. The preparation is allowed to dry; it is best not 
to do it over a flame. When dry the cover-glass is passed rather 
slowly three times through the flame of a Bunsen burner. This 
coagulates the albumin and prevents the material being washed 
off during the process of staining. The cover-glass is covered 
with the stain and gently warmed for fifteen to twenty seconds 
over a small flame. The specimen is then washed in water, 
dried by blotting and by gently warming, and mounted in 
balsam. 

Various of the anilin colors are the ones chiefly used in bac- 
terial staining. They may be used alone or in combination 
with certain reagents employed to increase the staining power. 

Saturated alcoholic solutions of the stains should be kept in 
stock, and from them the dilute aqueous solutions can be pre- 
pared. These latter, however, do not keep well, so various 
standard preparations are usually kept on hand. 

Lbffler's Methylene-blue. — 

Sat. ale. sol. methylene-blue 30 c.c. 

Caustic potash in water (1 : 10,000) 100 " 

This keeps a long time and stains rapidly. 
Neisser's Stain for Diphtheria. — 

Solution No. 1 

Methylene-blue 0.1 gm. 

Alcohol 2.0 c.c. 

Glacial acetic acid * 5.0 " 

Distilled water 95.0 " 

Dissolve the methyelene-blue in the alcohol and add it to the 
acetic-acid-water mixture. Filter. 

Solution No. 2 

Bismarck brown 0.2 gm. 

Water (boiling) 100.0 c.c. 

Dissolve the stain in the boiling water. Filter. To stain: 
Fix the preparation. Pour on the acetic-acid-methylene-blue 
solution and allow to act from thirty to sixty seconds. Wash. 
Then pour on the Bismarck-brown solution, and after thirty 
seconds wash off with water. Dry and mount. The bodies 



STAINING BACTERIA 207 

of the bacilli are brown, with dark blue spots at either end. 
Best results are obtained with cultures from nine to eighteen 
hours old. 

Carbol-thionin. — 

Sat. sol. thionin in 50 per cent, alcohol 10 c.c. 

Carbolic acid aq. sol. (2 per cent.) 100 " 

Carbolfuchsin. — 

Sat. ale. sol. fuchsin 10 c.c. 

Watery sol. carbolic acid (5 per cent.) 90 " 

This stain is very permanent and is useful for many pur- 
poses. It is employed in the differential diagnosis of tubercle 
bacilli. In this method (Ziehl-Nielson) the cover-glass or slide 
is covered with the above stain and heated until steam rises, 
for about three minutes. Care must be taken not to boil the 
stain and to replace the solution as it evaporates. Wash thor- 
oughly in water and then decolorize with about a 10 or 15 per 
cent, watery solution of nitric acid. Wash again in water, 
then in 95 per cent, alcohol for thirty seconds, and counter- 
stain for a minute in LorHer's methylene-blue. The tubercle 
bacilli will appear as minute red rods; all other organisms will 
be blue. 

Anilin Gentian-violet. — 

Sat. ale. sol. gentian-violet 16 c.c. 

Anilin water 84 " 

Anilin water is made by taking: 

Anilin oil 5 c.c. 

Distilled water 95 " 

Shake thoroughly until a milky fluid is obtained; then filter. 
This stain should be freshly prepared when needed, as it 
does not last more than ten days. 
Carbol Gentian- violet. — 

Sat. ale. sol. gentian- violet 1 c.c. 

Aq. sol. carbolic acid (5 per cent.) 10 " 

This solution is permanent, but tends to overstain. 



208 BACTERIOLOGIC METHODS 

Gram's Method. — After the cover-glass has been smeared 
and fixed it is stained in: 

i. Anilin or carbol gentian- violet thirty seconds. 

2. Washed in water two or three seconds. 

3. Put in Gram's solution, as follows, for thirty seconds: 

Iodin 1 gm. 

Potassium iodid 2 c.c. 

Water 300 " 

4. Washed in 95 per cent, alcohol until the color ceases 
to come out of the preparation. 

5. Dry by blotting and in air and mount in balsam. 

The value of this method lies in the fact that certain bac- 
teria will retain the stain, while others give it up. In those 
organisms retaining the stain there has been a combination of 
mycoprotein, anilin dye, and the iodids that forms a compound 
insoluble in alcohol. The bacteria stain dark blue or black, while 
the nuclei are only faintly colored. Nuclei that are undergoing 
division may stain rather deeply. 

An organism is said to stain by Gram's method when it is 
not decolorized. This power is made use of to differentiate 
certain organisms that may resemble each other in size and 
shape. 

The more important pathogenic bacteria are divided as 
follows, according to their reaction to Gram's: 

Stained by Gram's Method. Decolorized by Gram's Method. 

Staphylococcus pyogenes. Gonococcus. 

Streptococcus pyogenes. Bacillus typhosus. 

Streptococcus capsulatus. B. coli communis. 

Actinomycosis. B. of malignant edema. 

Bacillus anthracis. Spirillum of Asiatic cholera. 

Pneumococcus. Diplococcus intracellularis meningi- 

B. diphtherias, tidis. 

B. leprae. B. pyocyaneus. 

B. tuberculosis. B. of influenza. 

B. tetanus. B. of dysentery. 

B. aerogenes capsulatus. B. of bubonic plague. 

B. of glanders. 

Spirochaeta of relapsing fever. 



METHODS FOR STAINING SPORES 209 

METHODS FOR STAINING SPORES 

Spores are the resting forms of various organisms and are 
stained with difficulty, but when once stained are hard to 
decolorize. 

Abbott's Method — 

1. Stain the cover-glass deeply with methylene-blue, 

heating until the solution boils. 

2. Wash in water. 

3. Wash in 95 per cent, alcohol, containing 0.2 to 0.3 

per cent. HC1. 

4. Wash in water. 

5. Stain for eight to ten seconds in anilin-fuchsin solution. 

6. Wash in water, dry, and mount. 

The spores are stained blue; the bodies of the bacteria, red. 
Mbller's Method. — 

1. Wash the cover-glass for two minutes in chloroform. 

2. Wash in water. 

3. Place in a 5 per cent, watery solution of chromic acid 

for one-half to two minutes. 

4. Wash in water. 

5. Stain with carbolfuchsin for one minute, heating the 

solution slowly until it boils. 

6. Thoroughly decolorize in a 5 per cent, solution of 

sulphuric acid. 

7. Wash in water. 

8. Stain in aqueous methylene-blue (1 gm. to 100 c.c.) 

for thirty seconds. 

9. Wash in water, dry, and mount. 
The spores will be red; the bacteria, blue. 

The most satisfactory spore-staining method is really the 
negative staining of the spore obtained when a bacterial prepara- 
tion is stained by dilute carbolfuchsin or Loffler's methylene- 
blue. The spore appears as a highly refractile piece of glass in 
a colored frame. The acid-fast method, as for tubercle bacilli, 
gives good results, but the decolorizing must be lightly done, 
otherwise the spore will lose its red stain. 



2IO BACTERIOLOGIC METHODS 

STAINING OF FLAGELLA 

Lbffler's Method — 

i. Flood the cover-glass with the following solution, 
which should be filtered before using: 

Aqueous solution of tannic acid (20 per cent.) 10 c.c. 

Cold saturated solution of ferrous sulphate 5 " 

Saturated aqueous or alcoholic solution of gentian- 
violet or fuchsin 1 " 

This is very gently heated, not boiled, for about 
one minute. 

2. Wash in water. 

3. Stain in anilin gentian- violet or anilin-fuchsin with 

gentle heating thirty to sixty seconds. 

4. Wash, dry, and mount. 

Bowhill's Method. — Stain the cover-glass in the following 
solution, heating gently for ten to fifteen minutes: 

Saturated alcoholic solution of orcein 15 c.c. 

Aqueous solution of tannin (20 : 80) 10 " 

Distilled water 30 " 

Filter the mixture before using. The orcein stain should 
be at least nearly two weeks old. 

In staining sections for bacteria Gram's method or that 
used for the tubercle bacillus is generally employed. Better 
results are obtained with paraffin sections, but celloidin may 
be used. 

Staining Capsules. — 

1. Cover the preparation with glacial acetic acid for a 

few seconds. 

2. Drain off (do not wash) and replace with anilin gen- 

tian-violet. Pour this off and add more stain until 
all of the acid has been removed. 

3. Wash in a 2 per cent, solution of sodium chlorid 

and examine in the same. 



CHAPTER XIV 

SPECIFIC MICRO-ORGANISMS 

ORGANISMS OF SUPPURATION 

Inasmuch as suppuration, the formation of a purulent exu- 
date, is so common in connection with the majority of wounds, 
it seems advisable to start with this subject. Although the 
great majority of bacterial proteins will cause the formation 
of pus, there are certain bacteria which are usually found in 
these discharges; they are the micrococci. 

Staphylococcus Pyogenes Aureus, Albus, and Citreus. — 
These three forms of micro-organisms are similar in all their 
biologic properties, except that they produce different colors in 
their growth on artificial media. Many regard these as three 
races of the same species, probably a correct view. 

These pyogenic staphylococci are distributed very widely in 
nature, being found in dust, on the skin and mucous mem- 
branes, under the finger-nails, in the alimentary canal, and 
constantly in the mouth. Fortunately, in the great majority of 
cases the staphylococci isolated from the above sources are 
either very slightly virulent or totally avirulent. 

Pathogenesis. — As a rule, when infection occurs by these 
organisms the lesion is superficial and circumscribed, as ab- 
scesses, boils, and carbuncles, but deep-seated and widespread 
infections may result. They may enter the blood-stream and 
give rise to a purulent infection known as pyemia or to an ulcera- 
tive endocarditis. They are found also in the lesions of sup- 
purative pleurisy, pericarditis and peritonitis, and play an im- 
portant part in secondary infections. The staphylococci are 
associated frequently with the tubercle bacillus in pleurisy and 
suppurative meningitis, with the pneumococcus in pneumonia, 
and with the diphtheria bacillus in diphtheria. Osteomyelitis 



212 SPECIFIC MICRO-ORGANISMS 

may result from these organisms. In the human being boils 
and abscesses have been produced experimentally by rubbing 
cultures into the skin. In rabbits all forms of purulent in- 
flammation have been produced by inoculating staphylococci 
into various parts of the body. 

Immunity. — As yet no marked degree of immunity has been 
produced by the injection of antiserums or of cultures — living 
or dead. As the staphylococci form very little extracellular 
toxin, an antitoxic serum of any degree of strength cannot be 
obtained. Very good results in the treatment of staphylococcic 
infections have been obtained by the injection of bacterial 




Fig. 8i. — Staphylococcus Aureus. Fuchsin; X iooo (Giinther). 

suspensions of the same strain of coccus as caused the lesion. 
In this way the resistance of the individual is increased, and 
cases of acne and furunculosis have recovered rapidly when so 
treated. 

The Staphylococcus pyogenes aureus is the most important 
one of the group from a pathologic point of view, and may be 
used as the type. It is a non-motile, non-flagellate, non-spor- 
ogenous, liquefying, chromogenic, pathogenic, aerobic, and 
optionally anaerobic coccus, staining by the ordinary methods 
and by Gram's. It will grow at any temperature between io° 
and 44 C, but the optimum temperature is from 35 to 37 C. 



STREPTOCOCCUS PYOGENES 213 

Pigment production is most marked when grown between 20 
and 2 5 C. in the presence of oxygen. In cultures it produces 
fatty acids from sugars, forms indol, and is able to liquefy 
gelatin by the elaboration of ferments (diastases). It will 
coagulate milk and then gradually digest the casein. In cul- 
tures there is formed also a substance, leukocidin, which is 
destructive to white blood-cells, and one other that acts as a 
hemolysin. 

Cultures. — On gelatin plates this staphylococcus forms small 
orange-colored colonies which cause a surface liquefaction. 
The orange pigment is best seen in the center of the colony. 
In gelatin stabs it grows as a fine white line, developing its pig- 
ment in about three days. It liquefies the gelatin and forms 
an orange-colored precipitate. On agar there is considerable 
variation in color; is rarely golden, commonly being yellow or 
cream color. The colonies are moist, shining, and circumscribed. 
In bouillon the growth gives a diffuse cloudiness with a small 
amount of slightly yellowish sediment. In milk the growth 
causes an acid reaction, with coagulation and final digestion of 
the casein. On potato the most intense color is produced, the 
growth forming a more or less bright yellow, thick layer. 

Staphylococcus pyogenes albus has the same characteristics 
as the above, except that the growths are always white and 
the liquefaction of gelatin takes place a little more slowly. It 
is also less pathogenic. 

Staphylococcus pyogenes citreus, similar, except that it 
produces a lemon-yellow pigment. 

Staphylococcus epidermidis albus is habitually present on 
and in the deeper layers of the skin, and under certain condi- 
tions is able, probably, to cause pus formation. It is thought 
by many to be the S. pyogenes albus in an attenuated form. 

Streptococcus pyogenes is a non-motile, non-flagellate, non- 
sporogenous, non-liquefying, non-chromogenic, aerobic, and 
optionally anaerobic organism, pathogenic for man. It stains 
by the ordinary methods and by Gram's. It grows in chains 
of 4 to 20 or more individuals. 

Pathogenesis. — The streptococci are the primary cause of 
many inflammatory, suppurative, and septicemic conditions: 



2i 4 



SPECIFIC MICRO-ORGANISMS 



puerperal infection, erysipelas, endocarditis, meningitis, peri- 
tonitis, salpingitis, otitis, pneumonia, and cellulitis. Infec- 
tion by this organism seldom remains strictly localized. It is 
a matter of much interest and importance that recent in- 
vestigations indicate that acute rheumatism is due probably to 
this organism. As secondary invaders the streptococci may 
give rise to serious complications, particularly in scarlet fever. 
Cultures. — Grows best at 37 C. Does not grow luxuriantly 
on any culture-media, and must be transplanted frequently. 




t^.+ l ■ K &£ 9 » m 

"'"''■IUBf-,' - ■ JHfil. - **^ 




Fig. 82. 



-Streptococcus Pyogenes from the Pus taken from an 
Abscess. X 1000 (Frankel and Pfeiffer). 



On gelatin plates very small, colorless, translucent colonies appear 
in from twenty-four to forty-eight hours, without any lique- 
faction of the gelatin. In gelatin stabs a slightly opaque 
granular line is formed. On agar the growth is very delicate 
and transparent along the line of inoculation. The colonies 
are small and do not coalesce. In bouillon the cocci develop 
slowly. In milk the growth is more luxuriant, with the forma- 
tion of acid and eventual coagulation; the casein may then 
undergo digestion. On potato there is practically no growth. 



BACILLUS PYOCYANEUS 215 

Immunity. — By the injection of cultures of living virulent 
streptococci into horses a high degree of immunity has been 
obtained. This serum is probably both antitoxic and bac- 
tericidal in action. Many attempts have been made to cure 
streptococcic infections by the use of such serum, but the 
results have not been very satisfactory, no beneficial effect 
being obtained in many instances. The variations in effects 
probably are due to there being so many different strains of this 
organism. 

Coley's fluid consists of slightly acid bouillon in which a viru- 
lent streptococcus has been grown for three weeks, at the end 
of which time the flask is inoculated with Bacillus prodigiosus. 
After growing for some ten days more at room-temperature, 
the culture is shaken up, poured into bottles of about 20-c.c. 
capacity, and rendered sterile by heating to 50 to 6o° C. for 
one hour. The injection of this fluid into sarcoma is claimed 
to have caused necrosis and eventually a cure of the condition. 

In the growth of these bacteria there is formed a toxin that 
has a marked destructive effect on blood-cells. As killed cul- 
tures have a much more marked hemolytic effect than filtered 
ones, the important product must be an endotoxin. 

Bacillus pyocyaneus is an actively motile, flagellated, facul- 
tative anaerobic bacillus that liquefies gelatin. Is rather 
short and slender, 0.3 by 1 to 21 u. Stains by the ordinary 
methods, but not by Gram's. It is found in bluish or greenish 
pus, the color being due to products of its growth. 

Cultures. — It grows readily on all the ordinary culture-media 
at room and incubator temperatures. In the presence of 
oxygen two pigments are formed: the first, fluorescein, is a 
water-soluble green material that soon saturates the media, 
giving it the characteristic appearance. As the cultures be- 
come older a second pigment, pyocyanin, blue in color, is formed. 
On gelatin plates the colonies are small, irregular, slightly green- 
ish, and produce a distinct fluorescence of the adjacent gelatin. 
The gelatin undergoes liquefaction, forming crater-like ex- 
cavations. Gelatin stab cultures rapidly liquefy along the line 
of inoculation, with a saucer-like liquefaction at the surface, the 
medium turning greenish blue. On agar the growth develop- 



2l6 



SPECIFIC MICRO-ORGANISMS 



ing along the line of inoculation at first appears bright green. 
As the culture becomes older the second pigment forms, causing 
the medium to become a deep blue green or dark blue. In 
bouillon the organism produces a diffuse cloudiness and forms 
a thin pellicle or scum on the surface. In old cultures the bac- 
teria undergo autolysis and disappear. In milk the growth is 
luxuriant; the casein coagulated and then digested. The 

reaction becomes slightly acid 
for the first day or two, then 
alkaline. Upon potato a luxu- 
riant greenish or brownish, 
smeary layer is produced. 

In addition to the pigments 
this organism produces a curd- 
ling ferment, a fibrin- and 
casein-dissolving ferment, a 
gelatin- dissolving ferment, and 
a bacteriolytic ferment, the 
so-called pyocyanase. Under 
favorable conditions it may 
produce toxins that are fatal 
to guinea-pigs, the exotoxin 
endotoxin obtained by lysis of 




Fig. 83. — Gonococci in Urethral 
Pus (McFarland). 



being more virulent than the 
dead bacteria. 

Micrococcus gonorrhoeae, the gonococcus, is a non-motile, non- 
liquefying coccus found in pairs, with the opposed surfaces 
slightly concave. It measures from 0.8 to 1.5 ft in diameter. 
It is a purely parasitic organism and seems to be pathogenic 
for man only. 

Pathogenesis. — In man it gives rise to an acute purulent in- 
flammation of the mucous membranes of the urethra and 
genito-urinary tract in general, the vagina, uterus, fallopian 
tubes, and peritoneum. It is also the cause of ophthalmia 
neonatorum, the acute conjunctivitis of the newborn, and very 
commonly results in more or less complete blindness. The or- 
ganisms not infrequently gain entrance into the circulation, 
causing gonorrheal endocarditis (inflammation of the valves of 
the heart), pleuritis, and arthritis (inflammation of the joints). 



DIPLOCOCCUS PNEUMONIA 217 

The inflammation may extend from the urethra to the bladder, 
uterus, and kidneys. The toxic products of the gonococcus 
appear to be contained within the bodies of the bacteria and 
disseminated but slightly throughout the culture-media. The 
gonotoxin seems to be quite stable, not being destroyed by 
temperatures that are fatal to the cocci. Small quantities of 
this toxin when introduced into the urethra cause suppuration 
at the site of inoculation, fever, swelling of the neighboring 
lymphatic nodes, and muscular and articular pains. 

It stains by the ordinary methods, but not by Gram's. The 
relation of the cocci to the cells is quite characteristic. In 
most of the inflammatory exudates the gonococci are contained 
either in epithelial cells or in the leukocytes, very few lying 
free. This intracellular position is supposed to be the result of 
active phagocytosis by the cells, of the cocci. An important 
point in differentiating this diplococcus is that all the others, 
excepting the meningococcus, retain Gram's stain. This is of 
particular importance in medicolegal cases. 

Cultures. — Cultivation is difficult, as the organism does not 
grow upon any of the ordinary culture-media, and only scantily 
on any form of artificial medium. The optimum temperaure 
is 37 C., higher temperatures soon causing the growth to 
cease. The medium that has proved the most satisfactory is 
composed of ordinary nutrient agar to which about one-half the 
quantity of sterile hydrocele or ascitic fluid is added. On this 
medium, or on a tube of human blood-serum, the cocci in about 
twenty-four hours form small, isolated, thin, gray colonies that 
later become confluent and produce a delicate, smeary layer 
upon the medium. They must be transplanted every few days 
to fresh tubes, and even then soon lose their power of growth 
and cease to live. 

Attempts have been made to produce an artificial immunity, 
but as one infection does not confer immunity against further 
infection the results have not been successful. 

Diplococcus pneumoniae, or pneumococcus, is a minute, 
slightly lancet-shaped, non-motile, non-liquefying, optionally 
anaerobic diplococcus. It usually occurs in pairs, but short 
chains of from four to six may be found. In the tissues and in 



2l8 SPECIFIC MICRO-ORGANISMS 

sputum there is usually a distinct capsule present. This is not 
present, as a rule, when grown on artificial media, with the ex- 
ception of blood-serum. 

Pathogenesis. — This organism is the cause of lobar or croupous 
pneumonia, and is found in the lesions of that disease. That 
true pneumonia can be produced artificially has been proved by 
experiments made upon dogs, in which pure cultures of the 



\ 





♦ * 



Fig. 84. — Capsulated Pneumococci in Blood from the Heart 
of a Rabbit; Carbol-fuchsin, Partly Decolorized. X 1000 (Mc- 
Farland) . 

pneumococcus were injected into a bronchus. In addition to 
pneumonia, the diplococcus may cause pleuritis, meningitis, 
pericarditis, or peritonitis. In the early stages of pneumonia, 
before the crisis, the cocci may be recovered from the circula- 
tion by means of blood-cultures. 

"No thing definite is known about the metabolic toxic prod- 
ucts of the pneumococcus. That the symptoms of pneumonia 



BACILLUS PNEUMONIAE 210. 

are not entirely dependent upon the disturbance of respiration 
is clearly shown by the fact that the patients suffer from high 
fever and have marked leukocytosis with enlargement of the 
spleen. As filtered cultures are scarcely at all toxic, it is evident 
that the toxin must be purely or almost purely intracellular." 
This organism is peculiar in that it causes extreme fibrin forma- 
tion in the accompanying exudates. 

Although not found outside of the human body, pneumococci 
may be found, particularly in the winter months, in the saliva of 
some 30 per cent, of all people. That they are frequently viru- 
lent is evident, as when such saliva is injected into animals it 
often causes pneumococcic septicemia. 

Stains by the ordinary methods and by Gram's. 

Cultures. — Is killed by short exposure to low temperatures, 
by direct sunlight, and lives but a short time on ordinary 
culture-media. May live, however, in dried sputum or pus for 
several months. 

It grows best at 37 C, but has a range from 24 to 42 C. 
It will grow on all culture-media except potato, but best upon 
media that contain serum or hemoglobin. When grown in the 
presence of red blood-corpuscles there is no hemolysis such as 
is caused by the streptococci, and the colonies are greenish. 
On gelatin plates (15 per cent, gelatin) the colonies are small, 
round, circumscribed, finely granular white points which grow 
slowly, never attain any considerable size, and do not liquefy 
the gelatin. On agar the growth is slight and almost invisible; 
is more luxuriant if glycerin is present. In bouillon the organ- 
isms grow well, slightly clouding the medium. On blood-serum 
the growth is quite similar to that on agar. 

No immunity results from an attack of this disease; the 
individual's susceptibility may even be increased. Exposure to 
cold seems to predispose. 

Bacillus pneumoniae, Friedlander's bacillus, is an encap- 
sulated, non-motile, non-sporogenous, aerobic bacillus, short, 
and with rounded ends. May resemble a coccus. Varies in 
length, and sometimes occurs in chains of four or more indi- 
viduals. Stains by the ordinary methods, but is Gram- 
negative. 



220 SPECIFIC MICRO-ORGANISMS 

Pathogenesis. — Although this bacillus is not the usual cause 
of acute lobar pneumonia, it can give rise to an infection of 
the lungs that is very severe and often fatal. It can also cause 
severe purulent inflammations of the serous membranes, pleuri- 
tis, pericarditis, meningitis, and peritonitis. It can also cause 
septicemia in lower animals. It is frequently present in the 
saliva of many persons and appears to be widely distributed. 

This organism appears to be one of a group of bacteria known 
variously as the Bacillus lactis aero genes and the B. capsulatus 
mucosus. 

Cultures. — Grows best at body temperature and luxuriantly 
on all culture-media. In bouillon the medium becomes diffusely 
cloudy, with a pellicle on the surface and a viscid sediment in the 
bottom. On gelatin plates the colonies are round, slightly 
elevated, shiny, and yellowish white, with no liquefaction of 
the medium. Upon the surface of agar a luxuriant white or 
brownish-yellow, smeary, viscid, circumscribed growth occurs. 
Milk is not coagulated. On potato the growth is luxuriant, 
quickly covering the entire surface with a thick, yellowish-white 
layer. On blood-serum the growth is similar to that on agar. 

Diplococcus intracellularis meningitidis, or meningococcus, is a 
minute, non-motile, non-liquefying, non-chromogenic, strict 
aerobe coccus, usually found in pairs, but may occur in short 
chains. It very closely resembles the gonococcus in form, is 
nearly always found within pus-cells, and is decolorized by 
Gram's stain. Stains by the ordinary methods. 

Pathogenesis. — Is the cause of epidemic cerebrospinal menin- 
gitis, the organisms being present in the pus from the meninges, 
sputum, and nasal mucus of persons afflicted with the disease. 
In spinal puncture in this disease the organisms will be found in 
the pus-cells, and in this way a diagnosis can be made. The 
bacteria may also be found in the mucous membranes of healthy 
people, who in this way may be "carriers" of the disease. This 
organism very closely resembles the gonococcus, but neverthe- 
less belongs to a sharply differentiated species. The meningo- 
coccus is pathogenic for mice, while the gonococcus is not. The 
meningococcus when inoculated into the urethra will not cause 
an inflammation. Finally, the two organisms can be shown to 



MICROCOCCUS CATARRHALIS 221 

be different species by a study of the agglutination and com- 
plement fixation reactions. Very favorable results have been 
obtained in cases of this disease by injecting a serum obtained 
from animals inoculated with suspensions of meningococci. 
The serum is used by injecting it into the spinal canal through 
a lumbar puncture. The precaution must be taken to permit 
some of the fluid to escape first, and then replace it by the anti- 
serum, of which not more than 30 c.c. must be injected. This 
serum must be introduced into the spinal canal so as to come 
in direct contact with the cocci, as it is antibacterial and not 




Fig. 85. — Meningococcus in Spinal Fluid (from Hiss and Zinsser, 
"Text-Book of Bacteriology," D. Appleton & Co., Publishers). 

antitoxic in its action. The meningococcus produces an endo- 
toxin, but no soluble toxin. 

Cultures. — Grows best at 37 C, but is not easily cultivated. 
It will grow upon agar and glycerin-agar and upon Loffler's 
blood-serum. On agar plates the surface colonies consist of 
an opaque yellowish-brown center, around which a flat, rounded 
disk spreads out. The cultures must be transplanted fre- 
quently. 

Micrococcus catarrhalis is a coccus commonly found asso- 
ciated with superficial inflammatory conditions of the respira- 
tory tract and conjunctiva. It resembles the pneumococcus, 
but is Gram-negative. It is readily taken up by the leukocytes, 



222 SPECIFIC MICRO-ORGANISMS 

and may so resemble the gonococcus and the meningococcus 
that differentiation is difficult. The M. catarrhalis may, how- 
ever, be readily differentiated by the fact that it is easily cul- 
tivated, forming large white colonies, irregular in outline. It 
grows readily On all culture-media at room-temperature, best 
upon blood agar-agar. 

Micrococcus tetragenus is a large, round, encapsulated 
coccus, regularly associated in groups of four — tetrads. It 
stains by the ordinary methods and is Gram-positive. 

Pathogenesis. — The organism is pathogenic to mice, but 
under ordinary conditions does not affect man. The tetra- 
cocci, however, when present, probably hasten the tissue 
necrosis in tuberculous cavities, aid in the formation of ab- 
scesses of the lung, and contribute to the production of the 
hectic fever. 

Cultures. — It grows readily upon artificial media, does not 
liquefy gelatin. 

Bacillus tetani is a slightly motile, flagellated, spore-forming, 
liquefying, obligatory, anaerobic organism. It is found in 
earth, particularly that which has been manured, and in the dis- 
charges from wounds after infection. It is about 0.3 by 2 to 4 [i 
in size, usually rod-like, but frequently drum-stick shape on 
account of the presence of a large round spore situated at the 
end of the bacillus. It stains by the ordinary methods and is 
Gram-positive. 

Pathogenesis. — The most common method of infection is by 
penetrating wounds made by some instrument, nails, or splinters 
that have been in contact with infected soil, although the dis- 
ease may follow superficial and slight injuries. The nearer 
the wound is to the brain, as on the face or scalp, the more 
quickly will symptoms develop and the more probable is a 
fatal result. Inasmuch as the tetanus bacillus is a strict 
anaerobe, the presence of oxygen will hinder multiplication, 
but will not destroy the organism. Usually when the injury 
occurs pyogenic bacteria are present, and these, using up the 
oxygen, render conditions favorable for the accompanying 
bacillus. The injury to the tissue cells seems also to play an 
important role, as the Bacillus tetani is unable to gain a hold 



BACILLUS TETANI 223 

in normal tissue. The presence of necrotic tissue means -the 
presence of less oxygen, and also interferes with phagocytosis. 
It has been shown that if the tetanus spores be introduced 
into the body, after having been washed free from the toxin, 
they were unable to produce the disease because of the prompt- 
ness with which the phagocytes took them up. If, however, 
the toxin was not removed or the body cells injured, the spores 
would develop into bacilli, form toxin, and produce the disease. 




1 



Fig. 86. — Bacillus of Tetanus with Spores (Frankel and Pfeifier). 

When the organisms gain entrance into the body, under 
favorable conditions, they begin to multiply, form toxin, and 
in from three to nine days the symptoms will appear. The 
condition is due not to the presence of the organisms throughout 
the body, but to the toxin that is conveyed along the motor 
nerves to the motor areas of the central nervous system, the 
nerve-fibers and cells undergoing degeneration. Although the 
chief symptoms are due to nerve disturbances, some of the toxin 
does get into the circulation. This is shown by the fact that 
the blood of diseased animals is fatal to susceptible animals; 
also that the urine is likewise toxic when injected. 



224 SPECIFIC MICRO-ORGANISMS 

The muscles first affected are those that close the jaw, and 
then those of the back. 

Cultures. — This organism is cultivated with difficulty, as it 
will not grow where the slightest amount of free oxygen is pres- 
ent. It grows best at 37 C. When conditions are not of the 
best, spores form. These are very resistant, being able to with- 
stand 8o° C. for one hour; a temperature of ioo° C. for one 
hour being necessary to destroy them. In the growth there are 
formed various enzymes, one of which slowly liquefies gelatin, 
another ferments sugar. The most important product of growth 
is the toxin, which consists largely of tetanospasmin and tetano- 
lysin, both of which are soluble. The first produces convulsions, 
while the second destroys blood-corpuscles. The toxin is very 
unstable, being easily destroyed by heat above 6o° C. It is 
also quickly destroyed by light, particularly direct sunlight. 
By some the tetanus toxin is considered to be the most poison- 
ous substance known. 

In bouillon the medium is clouded, contains a sediment, and 
forms gas if sugar is present. On gelatin plates there is formed 
a rather dense, opaque central mass surrounded by a more 
transparent zone, the margins of which consist of a fringe of 
radially projecting threads of bacilli. At first white, the culture 
changes to yellow. Liquefaction takes place slowly. In gelatin 
stabs the growth occurs deep in the puncture and is arborescent 
or tree-like. Liquefaction extends slowly, but may involve the 
entire mass of gelatin and change it into a grayish- white, syrupy 
liquid. The growth in agar punctures is similar to that in gela- 
tin except that there is no liquefaction. In milk the organisms 
grow readily without causing coagulation. Also grow well on 
blood-serum, which is not liquefied. 

Immunity. — Although an active antitoxin can be obtained 
by injecting the toxin into animals, it has not proved to be as 
useful, clinically, as the diphtheria antitoxin. The reason 
for this has been pointed out by Nocard, who calls attention 
to the fact that the existence of tetanus cannot be known until 
a sufficient toxemia to produce spasms exists, and that, there- 
fore, it is impossible to attack the disease in its inception or to 
begin the treatment until too late to effect a cure. The anti- 



BACILLUS DIPHTHERIA 225 

toxin, however, has proved to be of immense value as a pro- 
phylactic. One of the most frequent causes of tetanus is the 
infection resulting from injuries due to blank cartridges or fire- 
crackers, the earth used in them being commonly infected 
with tetanus organisms. The accepted treatment at present 
is to lay open such injuries, cleanse them thoroughly, and inject 
the antitoxin. In this way the neutralization of the toxin can 
take place as it is formed and the patient be saved. Tetanus 
following vaccination against small-pox is usually due to infec- 
tion of the wound, and not to the presence of tetanus spores in 
the vaccine. 

Bacillus diphtheriae is a non-motile, non-liquefying, non- 
flagellate, non-sporogenous, non-chromogenic aerobic organ- 
ism from 0.4 to 1.0 (J. broad by 1.5 to 3.5 u long, slightly curved, 
and frequently with clubbed ends. The bacillus is peculiar in 
its pleomorphism (many forms), for among the well-formed 
individuals a large number of peculiar organisms are to be 
found, much larger than normal, some with one end enlarged 
and club shaped, some greatly elongated, with both ends en- 
larged. Distinct polar granules may be found at the ends of 
the bacilli. In addition to the pleomorphism, the variation in 
staining is characteristic. Some of the bacteria will contain 
deeply staining granules, others will have stained bands across, 
while many will stain solidly. With Neisser's method the 
polar bodies will stain deeply, while the body of the bacillus will 
be but slightly colored. The ordinary stains may be used, but 
the most characteristic results are obtained with Lofiier's 
methylene-blue. It also stains by Gram's method. 

Pathogenesis. — When introduced into the individual this 
organism, on mucous membranes, causes the formation of a 
pseudomembrane that consists chiefly of fibrin, but contains 
desquamated epithelium and the Bacillus diphtheriae. The 
common site is the upper respiratory tract, particularly the ton- 
sils. The toxin causes a local necrosis, and in that way gains 
entrance to the body, causing a marked and serious intoxication 
as a result of its absorption. In addition to the local disturb- 
ances there may be marked changes in the important nerves, 
nerve-centers, and in the parenchymatous cells of the kidneys, 
15 



226 



SPECIFIC MICRO-ORGANISMS 







Fig. 87. — Bacillus Diphtheria, 

Five Hours at 3 6° C. 
This shows only solid staining forms. 



1 -*i 






Fig. 88. — Bacillus Diphtheria, 
Same Culture, Eight Hours 
at 36 C. 

This also shows solid forms, 
many of them with parallel arrange- 
ment. 



5) 















Fig. 89. — Bacillus Diphtheria, 
Same Culture, Twelve 
Hours at 3 6° C. 






Fig. 90. — Bacillus Diphtheria, 
Same Culture, Fifteen 
Hours at 36 C. 



The bacilli stain faintly at their The bacilli stain more unevenly and 
ends, and in some small granules are the granules are larger, 

seen at the tip- of the faintly stained 
portions. 

(Photomicrographs by Mr. Louis Brown. The magnification is the 
same in all — X2000. All of the preparations were made from growth on 
blood-serum.) (Francis P. Denny, in "Jour, of Med. Research.") 



BACILLUS DIPHTHERIA 



227 



liver, and heart. Associated with the Bacillus diphtherias 
are both staphylococci and streptococci. These may give rise 
to complications such as endocarditis, pneumonia, and adenitis. 
Infection takes place by contact with persons suffering from 
the disease. It has been found, however, that a convalescent 
individual may harbor virulent diphtheria organisms for weeks 
or even months, and in that way be a source of danger to the 
community. 






r L 






• •$ W-i 



T 



\ 









f 



j. -v^ 



^ 



Fig. 91. — Bacillus Diphtheria, Fig. 92. — Bacillus Diphtheria, 
Same Culture as Figs. 87-90, Forty-eight Hours at 36 C. 

Twenty-four Hours at 36 C. This is the same bacillus as in 

This shows clubbed and barred Figs. 87-91, but from a culture 

forms as well as granular forms. At where the colonies were discrete. 

the lower part of the field is a paired It shows long filamentous forms. 

form which shows the characteristic 

clubbing of the distal ends. 

(Photomicrographs by Mr. Louis Brown. The magnification is the 
same in all — X 2000. All of the preparations were made from growth on 
blood-serum.) (Francis P. Denny, in "Jour, of Med. Research.") 

Cultures. — Grows on ordinary media at a temperature of 
37 C. Is quite resistant to drying, and has lived on culture- 
media for eighteen months at room- temperature ; also may 
remain alive in healthy throats for months. Light is detri- 
mental and an exposure of ten minutes to 58 ° C. kills it. 

The best medium is Loffler's blood-serum, on which the bac- 
teria form a smooth, smeary, yellowish-white layer at the end 
of twelve to eighteen hours when grown at a temperature of 



228 SPECIFIC MICRO-ORGANISMS 

37 C. To make a diagnosis of diphtheria a swab of absorbent 
cotton is brought in contact with the suspected surface and the 
tube is then inoculated directly. At the end of eight to ten 
hours there will be a growth sufficient for diagnostic purposes. 
If blood-serum media cannot be obtained, a hard-boiled egg 
with the shell removed under aseptic conditions makes a good 
substitute. The addition of 3 to 5 per cent, of glycerin to the 
solid media makes them more suitable. On gelatin plates the 
growth is not very good, the colonies appearing as small whitish 
points. The gelatin is not liquefied. On agar or glycerin-agar 
the colonies are slower to develop, but are larger and slightly 
raised in the center, with a flat surrounding zone that has in- 
dented -edges. In bouillon there is formed a distinct, whitish, 
granular pellicle which is very brittle. Milk is a very good 
medium. At first alkaline, the reaction becomes acid, but when 
the culture becomes old the reaction again becomes strongly 
alkaline. 

Immunity. — This may be the result of having had the dis- 
ease, or may be of the passive type obtained by injections of 
the antitoxin. When the organism grows it produces a power- 
ful toxin, which in favorable cases so stimulates the body cells 
as to cause the formation of an antibody which is found in 
the blood. Such a serum is obtained from horses and consti- 
tutes the diphtheria antitoxin. This may be used either as a 
prophylactic or a curative measure. The value of the antitoxin 
depends upon its use in the early stages, the earlier the better. 
Of those cases treated with this serum in the first three days of 
the disease there was a fatality of 8.5 per cent. If injected 
after the third day there was a fatality of 27.8 per cent. At the 
outset about 4000 units should be given. In the later stages 
8000 to 10,000 units should be injected every four to six hours 
until the characteristic effect, the freeing of the membrane, is 
produced. Except in very young children the age should not 
effect the dosage. In severe cases there should be practically no 
limit to the amount given, nearly 200,000 units having been 
used in some instances. Doses of from 600 to 1000 units may 
be used as a prophylactic in those who have been exposed to 
diphtheria. 



BACILLUS ANTHRACIS 229 

Bacillus anthracis is a non-motile, non-chromogenic, sporog- 
enous, liquefying, aerobic bacillus, from 1 to 1.5 ^ in breadth 
by 5 to 20 ft in length. It has square ends and is found either 
singly or in chains or long threads. It stains by the usual 
methods and by Gram's. 

Pathogenesis. — This organism is particularly deadly to cattle 
and sheep, and may give rise to fatal infection in man, when it 
is known as "malignant pustule." The bacilli usually enter 
the body through wounds, giving rise to a local lesion which 
may give rise to a general bacteremia. When they enter the 
circulation they multiply very rapidly, and possibly may 
mechanically overwhelm the animals by absorbing nutriment 
and oxygen and blocking the capillaries. There is very little 
toxic action exerted. In men handling wool the spores may be 
inhaled, giving rise to an infection of the lung. 

Cultures. — Grows readily on all media; best at 37 C, but has 
a range of from 14 to 45 C. Between the temperatures of 18 
and 4 1. 5 C. spores are formed if free oxygen is present; is most 
marked at 37 C. At this degree a small refractile point will 
appear within the protoplasm of the bacilli in the course of a 
few hours. This increases in size, is oval in shape, and is 
situated in the center of the bacillus without altering its shape. 
This is the most resistant form of the organism. The spores 
can withstand dry heat at ioo° C. for one hour, and are highly 
resistant to chemicals, light, and drying. 

On gelatin plates the colonies are very characteristic. They 
appear first as minute, round, grayish-white dots, which spread 
out into flat, irregular, transparent tufts like curled wool. 
From a tangled center large numbers of curls, made up of parallel 
threads of bacilli, extend upon the gelatin. As soon as the 
colony attains to any considerable size, liquefaction becomes 
rapid. In gelatin stabs the bacilli grow along the entire track 
of the wire, but develop best at the surface, where oxygen is 
plentiful. From the deeper growth fine filaments extend into 
the surrounding medium. On the surface there soon appears 
a cup-shaped area of liquefaction; this progresses downward 
until, finally, the entire gelatin becomes fluid. On agar after 
incubation for twenty-four hours a whitish streak appears; 



230 SPECIFIC MICRO-ORGANISMS 

this rapidly thickens, becomes rather dry and friable, and has 
lightly notched borders. It is not very characteristic. In 
bouillon a thick, felt-like pellicle forms, from which extensions 
descend into the clear bouillon below. In the course of time 
the growth ceases and the pellicle sinks to the bottom of the 
tube. In milk the organisms grow well, causing coagulation to 
take place toward the third or fourth day. The coagulum is 
redissolved about the end of the week, the reaction, which is 
acid, not being changed. Upon potato there appears after the 
second day a whitish deposit, which rapidly thickens and assumes 
a dull-white color, becoming brown on keeping. 

Immunity. — It is doubtful if the anthrax bacillus in its growth 
produces any important toxic substance. An animal that has 
recovered from an attack, however, is immune, and it is possible 
to immunize animals by means of vaccines. These are pre- 
pared by growing the bacillus at 42.5 ° C, at which point spores 
are not formed. The virulence of the organism soon diminishes 
until it is harmless to guinea-pigs and rabbits. If this at- 
tenuated culture be inoculated into a sheep the animal suffers 
from a very mild attack of anthrax, and, after it has recovered, 
it will be found to be capable of resisting the inoculation of a 
fully virulent organism. 

Bacillus oedematis maligni is a motile, flagellated, anaerobic, 
liquefying, non-chromogenic, sporogenous bacillus, 0.8 to 1 [i 
in breadth and 2 to 10 fi in length, with rounded ends. Stains 
by the ordinary methods, but is Gram-negative. 

Pathogenesis. — When introduced beneath the skin the bacil- 
lus is pathogenic for a large number of animals; cases have been 
reported in man with usually a fatal result. In order that in- 
fection should take place the organisms must be deep within 
the tissues so as to be protected from oxygen. The bacteria 
will be found mainly in the subcutaneous tissue and not in the 
blood. 

Cultures. — The organism is a strict anaerobe, but under such 
conditions grows freely at room or incubator temperature in 
most culture-media. On gelatin plates the colonies appear as 
small shining bodies with liquid, grayish- white contents. Under 
the microscope they appear filled with a tangled mass of long 



BACILLUS AEROGENES CAPSULATUS 23 1 

filaments. In glucose- gelatin stabs a globular area of liquefac- 
tion occurs, and marked gas production takes place. In 
bouillon a diffuse clouding appears, followed by the formation 
of a sediment. There is no surface growth. Milk is slowly 
coagulated. It also grows well upon the surface of agar, potato, 
and blood-serum when all free oxygen is absent. 

Bacillus aerogenes capsulatus is a large non-motile, non- 
rlagellate, non-chromogenic, sporogenous, purely anaerobic bacil- 
lus, 0.5 u broad by 3 to 5 u long, and with slightly rounded 
or square ends. It occurs in groups, pairs, or in chains, but is 
more slender than the anthrax bacillus. 

It stains by the ordinary methods and by Gram's. 

Pathogenesis. — The organism is found in the tissues in the 
necrotic areas. The disease-producing powers of this organism 
are distinctly limited, and although it may cause death, it 
appears to do so only when the affected individual is already 
debilitated. Being anaerobic, the bacillus cannot live in the 
circulating blood, but can grow in old clots and in cavities, 
such as the uterus, where little oxygen can enter. When it 
enters the body it causes an emphysematous destruction of the 
tissues before death, and the formation of a large amount of 
gas postmortem. After death has occurred the bacilli are no 
longer inhibited by oxygen in the blood, so there is much gas 
formed. 

Cultures. — Usually in the body-fluids and often in cultures the 
bacilli are surrounded by distinct capsules — clear, unstained 
zones. It grows on the ordinary media, but in glucose-gelatin 
shows best the characteristic gas production. Does not cause 
liquefaction, but the gelatin becomes softer. In deep stab 
cultures it produces small knot-like, grayish-white colonies 
from which extend fine hair-like or feathery projections. In 
agar the deeper colonies grow best and produce so much gas that 
the medium may be pushed to the top of the tube. In bouillon 
the growth is rapid, the medium becomes cloudy, and a frothy 
upper layer forms. After a few days the bacilli fall to the bot- 
tom of the tube, leaving the bouillon clear. The reaction be- 
comes strongly acid. In glucose bouillon the growth and gas 
formation is more luxuriant. In milk the growth is rapid and 



232 



SPECIFIC MICRO-ORGANISMS 



luxuriant, coagulation occurring in from twenty-four to forty- 
eight hours. On potato there is a thin, moist, and grayish-white 
growth, with bubbles in the fluid at the bottom and sides of the 
tubes. As this bacillus is strictly anaerobic, the above growths 
will not take place unless all free oxygen has been removed. 

Bacillus influenzae is a minute, non-motile, non-liquefying, 
non-chromogenic, aerobic bacillus. Is very small, about 0.2 by 
0.5 ft, usually found singly, but at times occurring in chains of 
three to four. 

Stains by the ordinary methods, but is Gram-negative. 




Fig. 93. — Bacillus of Influenza. Smear from Sputum (after Heim). 



Pathogenesis. — The organism is found in the discharges from 
the nose and from the bronchi of those having the disease. 
It has also been found in the blood. Although pathogenic for 
few laboratory animals, this organism can cause many mani- 
festations in the human being. Commonly causing bronchitis, 
and pneumonia, both croupous and catarrhal, it can give rise 
to abscess formation, particularly of the middle ear, with 
mastoiditis and meningitis. It may complicate true pneu- 



BACILLUS TYPHOSUS 233 

monias and thus seriously affect both old and young. In some 
cases it apparently gives rise to intestinal disturbances. On 
account of the marked general depression that accompanies 
infection it would seem that the organism must produce a 
powerful toxin. Xo immunity appears to result from infec- 
tion, the individual, indeed, seemingly becomes more susceptible. 
Cultures. — Is easily destroyed by light, drying, and heat; 
6o° C. for five minutes will kill. Grows best at 37 C. and is 
strictly aerobic. Grows vers- poorly on artificial culture- 
media, but develops best on media smeared with blood. After 
twenty-four hours the colonies appear as minute, colorless bodies, 




Fig. 94. — Bacillus Typhosus, from a T\yexty-four-hour-old Agar- 
agar Culture. X 650 (Heim). 

looking like dewdrops, but not coalescing. When grown to- 
gether with the Staphylococcus aureus the colonies of the bacil- 
lus grow to an unusually large size within twenty-four hours. 
This peculiarity seems to depend upon the action of certain 
substances secreted by the staphylococci or to some change 
induced in the medium as a result of their growth. 

Bacillus typhosus (Koch-Eberth bacillus) is a motile, flagel- 
lated, non-sporogenous, non-liquefying, non-chromogenic, aero- 
bic, and facultative anaerobic bacillus, 0.5 to 0.8 u broad by 
1 to 3 ft* long, with rounded ends. Seldom occurring in chains. 

Is stained by the ordinary methods, but is Gram-negative. 



234 



SPECIFIC MICRO-ORGANISMS 



Pathogenesis. — This organism is the cause of typhoid fever. 
Any doubt has been removed by the fact that the introduction 
of the dead organisms protects the individual from attacks of 
the fever. Outside of the body it is found in fluids, water and 
milk, that have been contaminated by discharges from infected 
persons. It is found in the urine and feces of patients, as well 
as in the blood, tissue lesions, and the gall-bladder. In this 
latter place the organisms may remain for many years (ten 
to thirty) after the patient has recovered from the attack. 
The infected person is evidently immune, but, as a "typhoid 
carrier," may be the source of infection to many others. 




Fig. 95. — Bacillus Typhosus, showing Flagella (McFarland). 

Cultures. — Grows upon all ordinary media at body tempera- 
ture. Is readily destroyed by heat, 6o° C. for ten to fifteen 
minutes killing it. It can, however, withstand long exposure to 
cold, remaining alive in ice for several months. In distilled 
water it may live for some months, provided no saprophytic 
organisms are present, in which case the typhoid bacilli soon die. 
Drying and exposure to sunlight soon kill. 

On account of the very close resemblance to the Bacillus coli 
communis much work has been done in devising methods by 



BACILLUS TYPHOSUS 



235 



which the two can be distinguished. On agar the colonies are 
not characteristic, being round, grayish white, and shining. In 
bouillon the only change produced is a diffuse cloudiness. 
The following are the chief differences between the two: 



Colonies on gela- 
tin plates: 



On potato: 



Milk: 



Peptone media: 

Ferments: 
Potassium nitrate : 

Conradi-Drigalski 

medium: 
Endo agar: 
Neutral red: 
Agglutination 

test, 
Widal reaction: 



B. TYPHOSUS. 

On surface large, thin, and 
bluish, with notched bor- 
der; yellowish brown in 
center. Deep colonies, 
brownish yellow and 
sharply circumscribed. 
Non-liquefying. Develop 
more slowly. 

Usually forms a thick, 
moist, and shiny invisible 
film. Sometimes yellow- 
ish or brownish. 

Slightly acidulated, but not 
coagulated. Diffuse 
cloudiness. 



No indol formation. 



No gas formed in media 

containing sugar. 
Not reduced. 

Blue, transparent colonies. 

Colorless colonies. 

Color remains red. 

Typhoid bacilli are clumped 
when acted upon by di- 
luted serum from the 
blood of typhoid pa- 
tients. 



B. COLI COMMUNIS. 

On surface large, yellow- 
brown, round or oval, 
with irregular border. 
Deep colonies, round, 
yellowish brown, ho- 
mogeneous. Non- 
liquefying. 



Luxuriant growth, 
lowish brown 
glistening. 



Yel- 
and 



Rapid coagulating and 
marked acidulation. 
Turns blue litmus 
milk red, colors entire 
medium. Marked tur- 
bidity. 

Indol formed within 
twenty-four to forty- 
eight hours. 

Fermentation whenever 
sugar is present. 

Reduced to nitrites and 
then to ammonia. 

Red, opaque colonies. 

Red colonies. 
Changes to yellow. 
No clumping. 



Immunity. — Following an attack of typhoid fever the indi- 
vidual is usually immune from further attacks for a long time. 
Excellent results in giving rise to an artificial immunity have been 
obtained by the injection of typhoid bacterins — solutions con- 
taining more or less definite amounts of killed typhoid bacilli. 
This method has been employed mainly in the armies through- 



236 



SPECIFIC MICRO-ORGANISMS 



out the world, and has, in many instances, apparently elim- 
inated this disease. 

As a result of infection by this organism there appears, at the 
end of from five to seven days, a substance in the blood-serum 
known as an agglutinin. An important test in the making of a 
diagnosis of typhoid fever, known as the Widal reaction, is 
based upon the principle that when the serum of a patient 
suffering from typhoid fever is added to a fresh culture of the 
typhoid organism, the bacilli will gather into clusters and 
gradually lose their motility, a process known as clumping. 




Fig. 96. — Agglutination of the Typhoid Bacillus by a Specific 

Serum. 



The reaction is performed as follows: The most satisfactory 
way is to obtain the blood in a fresh state, and if one can get a 
sufficient amount to allow of the use of the serum alone, it is 
even better. A drop of blood or serum is forced out of a capil- 
lary tube, in which it should be obtained, and to this 9 drops 
of sterile water are added. This is thoroughly mixed, and 
1 drop of this mixture added to 1 of the culture gives a dilu- 
tion of 1 : 20. It is generally recommended to use a bouillon 
culture not more than twenty-four hours old. Some authors 
recommend an agar culture, but there may be some difficulty 



BACILLUS COLI COMMUNIS 237 

in breaking up the masses of bacilli. Dilutions of 1 : 10 and 
1 : 50 also should be employed as control tests. The reason for 
diluting is that in the pure serum there may be substances that 
will cause agglutination for many bacteria, and, therefore, is 
not specific. A drop of the diluted serum and culture is placed 
on a cover-glass, which is then inverted over a hollow-ground 
slide. The cover should be held on with a ring of vaselin so as 
to prevent evaporation. The reaction is said to be positive 
if, within forty-five minutes, the bacilli are found to be 
gathered in little groups and their motility almost or entirely 
absent. 

If the blood cannot be sent in the fluid state, several drops 
of blood should be placed on a clean slide and, when dry, sent 
to the laboratory. One of the drops of blood is dissolved in a 
drop of sterile water, and then diluted until the proportion is 
approximately 1 : 500. 

Although this reaction usually appears within a week after 
the onset of the disease, it may be delayed until much later. 
It may be present as a result of a previous attack of typhoid 
fever, so one must be on guard lest a mistaken diagnosis be 
made. 

Paratyphoid Bacillus. — Under this heading are described 
certain organisms which in many respects resemble the typhoid 
and the colon bacilli. They are all Gram-negative motile 
bacilli which do not form spores or liquefy gelatin. Infection 
by them gives rise to a condition similar to typhoid fever, 
except that the clinical symptoms are usually much milder, 
and the intestinal lesions may be absent. The two chief varie- 
ties are the Paratyphoid A and the Paratyphoid B. 

Bacillus Coli Communis. — In its general characteristics it 
resembles the B. typhosus, and can be distinguished from the 
latter only by careful cultivation on special media. (See p. 235, 
under Bacillus typhosus.) 

Is stained by the ordinary methods, but is Gram-negative. 

Pathogenesis. — Normally, this organism is found in the feces 
of all animals, and in water that has been contaminated by them. 
In man it may act in a secondary role, but there are cases of 
appendicitis, peritonitis, and cystitis in which the colon bacillus 



238 SPECIFIC MICRO-ORGANISMS 

appears to have been the exciting agent. Suppurative inflam- 
mation of the bile-ducts has also been caused by it. It may give 
rise to terminal infections, those occurring shortly before death, 
and almost immediately after death it begins to penetrate the 
intestines, and is the most frequent contaminating micro- 
organism met with in cultures made at autopsy. 

Immunity. — It has been shown that the colon bacillus contains 
a toxin within the cell which under ordinary conditions does not 
diffuse from it into the culture-medium. When injected re- 
peatedly into animals it gives rise to the formation of agglutinins 
within their blood. As yet no antisera have been obtained that 
are of any value in colon infections, but much benefit has 
resulted from the use of bacterins. 

Bacillus pestis is a minute, non-motile, non-flagellated, non- 
sporogenous, non-chromogenic, non-liquefying, aerobic bacillus. 
Is very short, 1.7 by 2 ^, with rounded ends. Varies greatly in 
shape. 

Is stained by the ordinary methods, but is Gram-negative. 
The rounded ends stain more deeply than the middle, thus 
frequently giving an appearance of a diplococcus. 

Pathogenesis. — This organism is highly pathogenic for man, 
giving rise to the bubonic plague. Investigations would indi- 
cate that the disease begins in rats. When an infected rat dies 
the fleas leave it and pass on to other rats or else human beings. 
They then bite their host, and when so doing deposit fecal 
material on the skin. Plague bacilli are in these discharges, 
and as a result of rubbing the bite gain entrance into the person. 
From the localized injury the infection spreads to the adjacent 
lymph-nodes, with the formation of buboes (enlarged suppurat- 
ing lymph-nodes). General bacteremia with death commonly 
ensues. Sometimes, instead of skin infections, the bacilli may 
get into the lungs, causing pneumonic plague, the most fatal 
type. The bacilli will be present in the sputum. Practically 
all domestic animals are susceptible, particularly the rodents, 
as rats and squirrels. 

Cultures. — Grows well on artificial media at a temperature of 
37 C. Is easily destroyed by heat, 55 to 6o° C. for about 
ten minutes, exposure to sunlight for three to four hours, and 



BACILLUS OF KOCH-WEEKS 239 

weak antiseptic solutions soon destroy. In dried pus the or- 
ganism is more resistant, and may retain both its vitality and 
virulence for several weeks. In soil the bacillus remains alive 
for several months. In bouillon a more or less marked turbidity 
appears, and occasionally a pellicle is formed on the surface. 
If there is complete freedom from vibration, a typical stalactite 
growth will take place. On agar the bacilli grow freely in the 
form of transparent white colonies which cannot be distinguished 
from the colon group. On gelatin, rounded, granular, and yel- 
lowish colonies form, but they do not cause liquefaction. In 
stab cultures a yellowish, semitransparent growth forms on the 
surface, while a whitish streak marks the line of the stab. In 
milk the growth is poor and the medium is not coagulated. On 
potato the growth is slow and slight, consisting of a whitish or 
yellowish streak. 

Immunity. — Larger animals — as horses — have been immun- 
ized. Their serum contains specific agglutinins and bacterio- 
lysins as well as an antitoxin, and is capable not only of prevent- 
ing the disease, but also of curing it in mice and guinea-pigs, 
and probably in man. Haffkine, by injecting a bouillon culture 
that has been killed by exposure to 70 C. for one hour, has been 
very successful in protecting people against the plague. The 
immunity so obtained lasts about a month. 

Bacillus of Bordet-Gengou is the organism that experiment- 
ally has been proved to be the cause of whooping-cough. 
It occurs as very minute oval rods of about the same size 
as the influenza bacillus, 0.3 by 1.5 u. Is somewhat pleo- 
morphous. Is non-motile, non-sporogenous, and very difficult 
to cultivate primarily, but by subcultures growth can easily 
be obtained on ascitic agar, serum-broth, and blood-broth. Is 
a strict aerobe. 

The organisms do not stain readily and are Gram-negative. 

Bacillus of Koch-Weeks is the organism of acute contagious 
conjunctivitis ("pink eye"). Is a minute, slender bacillus, 
non-motile, non-flagellated, non-sporogenous, non-liquefying, 
non-chromogenic, aerobic, and optionally anaerobic. Stains 
by the ordinary methods, but is Gram-negative. Measures 
1 to 2 by 0.5 u. 



240 SPECIFIC MICRO-ORGANISMS 

In man a trace of a culture smeared on the conjunctiva gives 
rise to an acute conjunctivitis. 

The organism is aerobic and fails to grow, or grows very feebly, 
on the ordinary media, but on media containing blood or serum 
gives rise to a good growth at a temperature of 37 C. 

Bacillus Dysenteriae (Shiga). — A non-motile, non-flagellated, 
non-sporogenous, non-liquefying, non-chromogenic, aerobic, 
and optionally anaerobic bacillus. 

Stains by the ordinary methods, but is Gram-negative. 

Pathogenesis. — Shiga has come to the conclusion that the 
Bacillus dysenteriae is the specific cause of the epidemic dysen- 
tery common in Japan. Since then a similar organism has 
been found in epidemics in the United States. This bacillus 
seems to play an important part in the summer diarrheas of 
children, and has been isolated from the stools in such cases. 
It is also pathogenic for young cats, dogs, and guinea-pigs. 

Cultures. — Grows well on alkaline media at a temperature 
of 37 C. On gelatin plates the colonies are small and like dew- 
drops, with no liquefaction. In gelatin punctures the growth 
consists of crowded, rounded colonies along the line of inocula- 
tion, with a grayish-white growth upon the surface. Quite 
closely resembles the growth of the typhoid bacillus. On agar 
large solitary colonies develop at the end of twenty-four hours. 
They are bluish white and rounded. In milk there is at first 
slight acid formation, then the medium becomes alkaline, but 
no coagulation takes place. On potato the growth is like that of 
the typhoid bacillus, but at the end of twenty-four hours be- 
comes yellowish brown. In bouillon there is a diffuse growth 
after twenty-four hours. This gradually sediments until the 
upper part of the tube is clear. No pellicle is formed. In 
peptone solution no indol is formed. 

Bacillus tuberculosis is non-motile, non-flagellate, non-spo- 
rogenous, non-liquefying, non-chromogenic, non-aerogenic, dis- 
tinctly aerobic, and acid resisting. It commonly occurs in the 
form of slender, slightly curved rods with rounded ends, not 
infrequently showing branches. For this reason it may not be 
a bacillus, but an organism belonging to the higher bacteria. 
It measures from 1.5 to 3.5 u by 0.2 to 0.5 [i. 



PLATE i 



9) 







Tubercle Bacilli from Specimen of Sputum. (From Bonney, " Pul- 
monary Tuberculosis.") 

Bacilli red, other organisms and tissues blue. The so-called attenuated 
variety of tubercle bacilli. Note the elongated rods, some of which are 
notched and beaded. Note also faintness and irregularity of stain. 



BACILLUS TUBERCULOSIS 24 1 

Staining. — This bacillus belongs to a group of organisms 
known as "acid fast," on account of their ability to resist 
decolorization by acids. The tubercle bacillus is very difficult 
to stain, and special methods have to be employed. This resist- 
ance to staining is probably due to a surrounding capsule that 
consists of a fatty or waxy substance, inasmuch as it can be 
colored by the fat stains, such as Sudan III. Under some con- 
ditions this bacillus may not possess its acid-fast properties, 
yet when inoculated into animals the same organisms will 
produce tuberculosis, and acid-fast bacteria will be found. 

The following method, that of Ziehl-Nielson, is commonly 
employed for staining tubercle bacilli, particularly in sputum. 
After having made, dried, and fixed the smear, the cover-glass 
or slide is covered with carbolfuchsin (saturated alcoholic solu- 
tion of fuchsin 10 c.c, 5 per cent, watery solution of carbolic acid 
90 c.c.) and carefully heated, until steam rises, for some three 
or more minutes. Care must be taken not to boil the stain 
and to replace the solution as it evaporates. Then wash the 
smear thoroughly in water and decolorize with about a 10 to 
15 per cent, solution of nitric acid in 95 per cent, alcohol. 
Will take about thirty seconds to a minute. Wash again in 
water and counterstain in Lorrler's methylene-blue. Wash 
and examine. The tubercle bacilli will appear as minute red 
rods; all other organisms and cells will be blue. 

With Gram's method the bacillus retains the stain. 

Pathogenesis. — Experiments and investigations carried on 
all over the world since the time of Koch's announcement have 
proved conclusively that this is the organism which gives rise 
to tuberculosis. There are possibly several types of the organ- 
ism, but those producing the disease in human beings and in 
cattle are the two most important. Those causing the disease 
in birds, reptiles, and fish need not be discussed. The disputed 
point in question at present is whether or not the bovine type 
can give rise to human tuberculosis. There has been much 
argument for and against, but it seems to be proved that human 
beings can be infected. There are cases on record where tuber- 
cles have developed on the hands after performing autopsies on 
diseased animals. It is quite probable that many of the cases 
16 



242 SPECIFIC MICRO-ORGANISMS 

in children of tuberculosis of the cervical lymph-nodes are due 
to infection acquired from the use of tuberculous milk. It is 
also probable that the intestinal tuberculosis of children is due 
to the bovine type of bacillus in many instances. 

Cultures. — This bacillus only grows in artificial cultures, 
provided that the medium contains serum, glycerin, yolk of 
egg, or fragments of tissue. It is an aerobic organism and 
grows only at temperatures above 30 C. In the case of 
human tubercle bacilli growth ceases at 41 ° C, and in the case 
of the bovine-bacilli, at 44 to 45 ° C. The optimum tempera- 
ture is 38 C. In order to obtain a pure growth it is best to 
first inoculate a guinea-pig with the suspected material. In 
the course of a couple of weeks the lymph-nodes will be en- 
larged, due to the disease. These should be removed with 
aseptic precautions, portions carefully taken, and culture-tubes 
be inoculated. Many tubes should be used, as some will either 
show no growth or else may be contaminated. 

After inoculating blood-serum the growth will be apparent to 
the naked eye after about twelve days in the form of small, 
white, round, scaly, dry looking colonies scattered over the 
surface of the medium. On further incubation the colonies 
become raised, but maintain their scaly appearance, and the 
margins are irregular in outline. This medium is not very 
satisfactory and is not much used. 

Glycerin-agar, except for primary cultures, is the best medium 
upon which to grow the bacillus, particularly if a little glucose 
be added. The growth begins as on serum, but the colonies 
are both larger and more numerous. They rapidly become 
confluent, and form a thick, whitish, dry, rough, scaly layer. 
After being subcultivated a few times the growth becomes very 
abundant, moist, and greasy. When old the growth has a red- 
dish tint. On bouillon containing glycerin and glucose the 
growth takes place in the form of a pellicle, which is dense, 
creamy white, dry, and very friable. The fluid remains clear, 
although the pellicle may eventually break in pieces and fall to 
the bottom of the tube. The organism will grow also on 
glycerinized potato and on Dorsett's egg-medium. This latter 
consists of the whites and yolks of eggs mixed, coagulated, and 



BACILLUS TUBERCULOSIS 243 

sterilized by the intermittent method. Gelatin cannot be used, 
as it melts at the temperature (37 to 38 ° C.) required for 
growth. During incubation the tubes should be closed, so as 
to prevent evaporation. 

Immunity. — Koch noted that by injecting killed cultures of 
the tubercle bacilli, after inoculation with living bacteria, the 
infected guinea-pigs improved in condition, and continued to 
live much longer than those animals not injected secondarily. 
He also discovered that a 50 per cent, glycerin extract of the 
cultures of the tubercle bacillus — tuberculin — produced the 
same effect as the dead cultures originally used. He announced 
the discovery of this substance in the hope that the prolongation 
of life observed to follow its use in the guinea-pig might also be 
true of man. Tuberculins obtained in various ways have been 
employed very extensively, with varying degrees of success. 
Some observers believe that the method is a very valuable one, 
while others claim that it is of little use. The tuberculin, 
when injected into persons suffering from chronic tuberculosis, 
is supposed to stimulate the formation of antibodies that will 
prevent further infection. 

Tuberculin is much used in determining the presence or 
absence of tuberculosis. The more. common methods are: 

The von Pirquet reaction: In this a drop or two of Koch's 
old tuberculin is placed upon the skin, and a small scarification 
made through the drop with a sterile lancet. If the person is 
tuberculous, a small papule develops at the point of inoculation 
that is not unlike a vaccine papule. It is at first bright, then 
dark red, and remains for a week. 

The Morro test consists in using the tuberculin in the form of 
a 50 per cent, ointment, made by mixing equal parts of "old 
tuberculin" and lanolin. This is rubbed into the skin without 
previous scarification. 

Calmette's reaction, the " ophthalmotiiberculin" test, consists 
of dropping 1 drop of a solution of prepared tuberculin into 
the eye of the suspected person. If no tuberculosis exists, no 
reaction occurs, but if the patient have tuberculosis, the eye 
becomes reddened within a few hours, and soon shows all the 
appearances C»f a more or less pronounced acute mucopurulent 



244 SPECIFIC MICRO-ORGANISMS 

inflammation of the conjunctiva. This attains its maximum in 
six or seven hours, and entirely recovers in three days. It 
usually causes the patient very little discomfort, but as a num- 
ber of patients have suffered from supervening corneal ulcera- 
tion and other destructive lesions of the eye, the test is now 
rarely used, the skin reactions being employed. 

Attempts have been made to obtain an antituberculous serum 
by injecting animals with either dead bacilli or tuberculin. 
The results, however, have not been satisfactory, the serums 
seeming to have neither curative nor prophylactic value. 

Bacillus leprae is non-motile, non-flagellate, non-sporogenous, 
chromogenic, non-liquefying, non-aerogenic, aerobic, and acid 
resisting. It very closely resembles the tubercle bacillus in 
size and shape. It stains in very much the same way as the 
tubercle bacillus, but is not so resistant. Ordinary methods 
can be employed. It is more easily decolorized, however, by 
acids. With Gram's method it stains well. 

Pathogenesis. — This is the organism that produces leprosy 
in man and monkeys; possibly in some of the lower forms of 
animals as well. The bacilli are found throughout the tissue 
lesions, and have been recovered from the blood of leprous 
individuals. 

Cultures. — For many years attempts to grow this organism 
were unsuccessful, but recently bacteria believed to be the true 
bacilli of leprosy have been grown on artificial media. This is 
doubted by some investigators. The organisms obtained are 
acid fast, and in many respects resemble those found in the 
tissues. Others, however, may be classed among the diphther- 
oid, on account of their similarity to the Bacillus diphtherial. 

According to Duval, the most successful method is as fol- 
lows : Egg-albumen or human blood-serum is poured into sterile 
Petri dishes and dried for three hours at 70 C. The excised 
leprous nodule is then cut into thin slices, which are distributed 
over the surface of the coagulated albumen. By means of a 
pipet the medium is bathed in a 1 per cent, sterile solution of 
trypsin. The Petri dishes are now placed in a moist chamber 
and incubated for a week or ten days. The bits of tissue soften 
to a thick, creamy consistence and the bacilli multiply enor- 



ACTINOMYCES FARCINICA 245 

mously. They may then be transferred to serum-glycerin-agar 
or to ordinary agar plus 1 per cent, of tryptophan. The colonies 
on these media are moist and orange colored. 

Actinomycosis. — The Actinomyces bovis, or ray fungus, is 
a non-motile, non-flagellated, liquefying, facultative, anaerobic, 
branched micro-organism belonging to the higher bacteria — 
the fungi. 

The organism is large enough to be seen by the naked eye, 
appearing as small yellow particles. The fungus is made up of a 
central mass of granular substance in which are many struc- 
tures resembling chains of cocci or spores. Extending from this 
center are many mycelial threads, terminating in club-shaped 
extremities. 

It stains by the ordinary methods and by Gram's. 

Pathogenesis. — This organism causes in cattle the disease 
known as "lumpy jaw" or "wooden tongue." The disease 
may be communicated to man, the infection supposedly taking 
place by means of spores gaining entrance by inhalation, by 
food, or, what is probably more common, by way of decayed 
teeth. 

Cultures. — It grows readily upon all the artificial media; best 
in the presence of air at a temperature of 37 C. On gelatin 
it grows feebly. Liquefaction takes place slowly and to a very 
slight extent. The colonies are small, grayish, and punctiform, 
with yellow centers and irregular outline. On glycerin-agar the 
growth appears after two days, and takes the form of small, 
yellowish- white, dry, wrinkled colonies, firmly adherent to the 
medium. These soon run together and form a broad, yellowish, 
wrinkled band, covered with rough projections. On blood- 
serum the colonies are small, whitish or yellowish, dry, firm, and 
often confluent. In glycerin broth white, granular, hemispheric 
colonies appear, and may grow as large as a pea. These fall to 
the bottom of the tube, leaving the medium quite clear. There 
is no surface growth. Does not coagulate milk. On potato 
small, colorless colonies appear in about a week. 

Actinomyces farcinica and Actinomyces madurae are two 
forms quite closely resembling the A. bovis, the first being 
pathogenic to the lower animals, the latter giving rise in man to 



246 



SPECIFIC MICRO-ORGANISMS 



madura-foot, an affection characterized by induration, ulcera- 
tion, and suppuration, with the formation of pus. 

Treponema pallidum (Spirochceta pallida) is an organism that 
is generally conceded to be the cause of syphilis. It has been 
found, by observers in all parts of the world, in the lesions of the 
primary and secondary stages; it is constantly present in the 
lesions of congenital syphilis ; it is found in the blood of persons 
suffering from syphilis; and it is never found either in healthy 
individuals or in persons suffering from diseases other than 
syphilis. This organism is very delicate, actively motile, non- 



m 




c V W^V' 



A &£ 




w & 



14 « 

/\i k y\ 



mm 




WM 



Fig. 97. — Syphilis, Congenital. Heart (Mallory). 
Treponemata pallida in connective tissue and between muscle-fibers. 



refracting, is long, thin, spiral or corkscrew shaped, with 
pointed ends. When stained they measure from 6 to 15 ft long 
by 0.25 fJ. across. Occasionally much longer forms are encoun- 
tered, but these consist of several parasites attached to each 
other end to end. They show from six to fourteen turns, which 
are short, clear cut, and regular. Extremely delicate flagellar 
have been demonstrated at the ends. No undulating membrane 
has been seen. 

This organism stains with difficulty and, as a rule, very 
lightly; consequently, special methods have to be employed. 
In smears the best results are obtained with Giemsa's or Roman- 



SPIROCH^TA REFRINGENS 247 

owsky's solutions. In tissues, Levaditi's method of nitrate of 
silver and pyrogallic acid gives beautiful results in formalin-fixed 
specimens, the treponemas staining black; the tissues, yellow. 
The most rapid and perhaps the most reliable method for find- 
ing the treponema is the examination with dark-ground illumina- 
tion. Special apparatus is needed for this. The treponemas 
will stand out brightly against the black background of the 
preparation and are easily seen. Is Gram-negative. 

Pathogenesis. — This organism is, without doubt, the cause 
of syphilis. As stated above, it has been found in the various 
lesions of the disease, and, now that it can be cultivated, Koch's 
postulates can be fulfilled. The disease has been reproduced 
experimentally in the higher forms of apes. 

Cultures. — Until recently the treponema could not be culti- 
vated artificially, but Noguchi has succeeded by using special 
methods. By inoculating syphilitic material into the testicles 
of rabbits he was able to get rid of contaminating organisms. 
Portions of this tissue are later transferred to a medium that 
consists of 1 part serum with 3 parts distilled water. The 
tubes are then incubated under anaerobic conditions. The 
treponemas begin to multiply after about forty-eight hours, 
and continue to increase slowly for four to five weeks. They 
attain their natural size in ten to twelve days, and later elongate 
and form tangled masses. 

Diagnosis. — The method devised by Wassermann of apply- 
ing the complement fixation-test has been used very success- 
fully in diagnosing this condition. It has been determined 
that if a hemolytic system be added to a mixture of extract of 
syphilitic liver, heated syphilitic serum, and complement, no 
hemolysis occurs. The method is described fully under the 
heading of Wassermann Reaction (see p. 268). 

Spirochaeta Refringens. — This organism is very commonly 
associated with the Treponema pallida in the syphilitic lesions, 
but can be distinguished readily. It is larger and longer, and 
in the fresh condition is highly refractile. The turns of the spiral 
are fewer, longer, less regular, and flattened. The impression 
given is that of a piece of ribbon. Its movements are more 
rapid than those of the Treponema pallida, and it stains easily 



248 SPECIFIC MICRO-ORGANISMS 

with the ordinary dyes, and colors blue with Giemsa's solution 
instead of red or pink. 

Spirochaeta balanitidis has been found in cases of ulcerative 
balanitis, and would appear to be identical with the S. refringens. 

Spirochaeta plicatilis is a large, thick spirochete which stains 
easily. The curves are widely separated and large, and an 
undulatory membrane is present. 

Spirochaeta Dentium. — This spirochete multiplies in carious 
teeth, and more closely resembles the Treponema pallidum than 
any other species. In common with the treponema it is an 
organism of very delicate structure, only slightly refractile in 
the fresh condition, and the turns of the spiral are regular and 
permanent. It is, however, shorter than the treponema, its 
average length being 4 to 10 ft, and the turns of the spiral are 
closer together and not so deep. It also stains more easily than 
the organism of syphilis. According to Noguchi, there are at 
least two varieties: the S. microdentium and the S. macrodentium, 
the former being the one that resembles the syphilitic organism. 
In making smears for staining or for dark-field illumination, 
when the lesions are in the mouth, great care must be observed 
in order to prevent mistakes in diagnosis. 

Spirochaeta buccalis is a large organism with few undulations. 
Stains easily, and should give no difficulty in distinguishing 
between it and the Treponema pallidum. 

Spirochaeta Vincenti. — This spirochete, found in association 
with the fusiform spirilla (see p. 171), has the same characters 
as the S. buccalis. It must be regarded as either very closely 
related to, or identical with, that organism. 

Treponema pallidulum (Spirochceta pertenuis) is an organism 
very closely related to that of syphilis. It is the cause of 
frambesia, or yaws, a contagious and inoculable disease very 
common in the tropics, and characterized by papillomatous 
lesions that do not involve the mucous membranes. 

Blood Spirochetes. — Several forms of spirochetes have been 
noted as giving rise to the disease known as relapsing fever. 
At present the spirochetes found in this disease in different parts 
of the world are considered as belonging to different species, of 
which the following are distinguished: 



SPIRILLUM CHOLERA ASIATICS 249 

Spirochceta recurrentis (obermeieri) , the organism of European 
relapsing fever. 

Spirochceta duttoni, the organism of West African relapsing 
fever (tick fever). 

Spirochceta novyi, of the American type. 

Spirochceta carteri, of East Indian fever, probably closely 
related to S. recurrentis. 

If a drop of blood be taken during an attack of fever, numerous 
spirochetes will be seen between the red cells of the blood, 




Fig. 98. — Cholera Spirilla, showing Flagella CMuir and Ritchie). 

8 to 10 ^ long, very slender, and pointed at the ends, each show- 
ing six to fifteen spirals. They are highly motile. 

These organisms are taken into the body of biting insects and 
then transmitted to healthy individuals when bitten by the in- 
fected individual. Bedbugs, lice, and ticks may act as the carriers. 

Spirillum cholerae asiaticae is a motile, flagellated, non-spo- 
rogenous, non-chromogenic, liquefying, aerobic, and facultative 
anaerobic spirillum occurring in the form of short arcs, spirals, 
and "comma" forms. Is about 0.8 u long, with one terminal 
flagellum. 

Stains by the usual methods, but is Gram-negative. 



250 SPECIFIC MICRO-ORGANISMS 

Pathogenesis. — This organism is found in the feces only of 
those suffering from Asiatic cholera, and apparently gives rise 
to the symptoms of the disease on account of the liberation of an 
endotoxin. Filtrates from young cultures are said to be non- 
toxic, but in old cultures the bacteria are broken down by the 
formation of a bacteriolytic substance and the endotoxins 
set free. In guinea-pigs a peritonitis can be caused by the 
injection of the organisms into the abdominal cavity. 

Cultures. — The cholera organism is easily destroyed by dilute 
chemical disinfectants; by light, heat, and drying; 6o° C. for 
ten minutes kills. Large amounts of indol are formed in peptone 
solutions. It grows at all temperatures between 12 and 40 C, 
but best at 37 C. It grows on all the ordinary neutral or 
slightly alkaline media and ferments sugars. On gelatin plates 
the colonies are characteristic, and appear in the lower strata 
of the gelatin as small white dots. These slowly extend to the 
surface, causing liquefaction. In gelatin stabs small colonies 
appear along the line of inoculation. Liquefaction extends 
slowly from the surface downward, giving rise to an inverted 
cone with an air-bubble at the upper portion. The medium 
finally becomes completely liquefied. On agar there is a 
copious whitish growth which develops rapidly, but has no 
characteristic features. On serum the growth is rapid and the 
medium soon liquefies. In milk, acid is formed and the medium 
sometimes coagulated. On potato there is no growth unless the 
reaction is alkaline; then a thick, clear, brown streak is formed. 

Immunity. — One attack of cholera usually leaves the indi- 
vidual immune. Haffkine has been able to bring about an im- 
munity that seems to be followed by a positive diminution of 
mortality in protected cases. His method consists in the giving, 
subcutaneously, of a single inoculation of a virulent organism 
recently recovered from the peritoneum of a guinea-pig. The 
injection of bacterial extracts has also been employed. It was 
with the cholera vibrio that PfeifTer was the first to demon- 
strate the bactericidal and agglutinating properties of the 
serum of immunized animals in vivo. 

Spirilla resembling those of cholera are the following. They 
are found in water, and although in many cultural respects 



BACILLUS FUSIFORMIS 25 1 

resemble the spirillum of cholera, they are not pathogenic to 
man, and will not agglutinate with serum from an individual in- 
fected with cholera. 

Finkler-Prior Spirillum. — Similar in shape, but shorter and 
stouter. Is actively motile. Grows rapidly, but does not 
produce indol; yet causes extensive liquefaction of gelatin. 
Is found in the feces of cholera morbus. 

Vibrio Tyrogenum. — Similar in form. Growth and liquefac- 
tion faster than in Spirillum cholerae, but less rapid than the 
Finkler. Is actively motile. Forms yellow, irregular, dis- 
tinctly circumscribed colonies. Is found in old cheese. 

Vibrio metchnikovii is a spirillum closely resembling that of 
cholera. Growth very similar to that of cholera, but is slower. 
Is found in the feces in chicken-cholera. Is pathogenic for 
chickens, pigeons, and guinea-pigs. 

Bacillus fusiformis is a long, rod-shaped organism measuring 
5 to 10 by 0.6 to 0.8 u, slightly swollen in the middle, and 
pointed at the ends. It stains readily with the ordinary dyes. 
The majority of observers state that it is Gram-negative, but 
others believe it to be Gram-positive. It is nearly always asso- 
ciated with the Spirochceta vincenti (see p. 248). 

Pathogenesis. — This organism was described originally as 
occurring in cases of hospital gangrene. It is more common 
at present in the form of Vincent's angina (see p. 179), an in- 
flammatory condition of the throat. 

Cultures. — It has been obtained in pure culture by growing 
upon the surface of ascitic fluid agar under strictly anaerobic 
conditions at 37 C. After two or three days the fusiform 
bacilli appear in the form of delicately whitish colonies, resem- 
bling colonies of streptococci. It has also been grown on rab- 
bit's blood agar, and on Loffler's blood-serum. From all of the 
cultures a somewhat offensive odor is given off. 

Many observers believed for a long time that the Bacillus 
fusiformis and Spirillum vincenti were but different stages of the 
same organism. This has been finally proved by Tunnicliff, 
who found that in pure cultures of the fusiform bacillus, after 
forty-eight hours, there appeared spiral organisms resembling 
those seen in smear preparations from the original source 



CHAPTER XV 

INFECTION 

By infection is meant the successful invasion of the tissues 
by an organism. The mere presence of the living agent within 
the body is not sufficient to cause infection; it must enter the 
tissues and give rise to symptoms that indicate a diseased con- 
dition. Trypanosomes may be even within the blood-vessels 
of certain animals and cause no symptoms. 

There are normally many organisms contained within the 
body, particularly in the alimentary canal, but they give rise to 
no pathologic conditions until they leave their accustomed 
habitat. 

Infection, therefore, means the entrance of organisms into 
the body, with subsequent injury to the tissues involved. 
By an infective disease is meant one that is the result of the 
entrance into and the multiplication of the organisms within 
the body. 

The symptoms in such a condition are the result of the 
formation of toxins, and not of mechanical disturbances. As 
a rule, no symptoms appear immediately after the entrance of 
the invading organism into the body, as there is not sufficient 
toxin present. The interval between the inoculation and 
the symptoms resulting from the toxins is known as the period 
of incubation, which differs greatly in different diseases. 

Then, too, infection may be influenced by certain peculiari- 
ties of the infecting organism and of the attacked individual. 
It is a well-recognized fact that true infection does Tiot always 
occur after the primary invasion. This may be due to varia- 
tions in the ability of the micro-organism to produce disease. 
Some have very little power to multiply after gaining entrance 
into the tissues, but they may form large amounts of poison. 
Other bacteria may form but little poison, yet have almost 
252 



INFECTION 253 

unlimited powers of multiplication when in the body. The 
number of the organisms and the mode of entrance also effect 
the severity of the infection. 

The infecting organisms may come from outside of the body — 
exogenous. They may enter the lungs in consequence of impure 
air or they may gain entrance into the body along with the food 
or water. Wounds of various sorts may carry the organisms 
into tissues; then, too, it has been discovered that diseases may 
be conveyed from one person to another by biting insects. 

Endogenous infections are those resulting from organisms 
that are commonly present within the body. They may be due 
to some change in the tissues of the host, that allow these living 
bodies to escape from their normal surroundings and gain 
entrance into unusual localities. The colon bacillus that is 
normal in the intestinal canal may cause much trouble if it gets 
into other localities. It must be remembered that practically 
all openings communicating directly or indirectly with the ex- 
ternal air will contain bacteria. They are normally present in 
the skin and the adjacent mucous membranes. The mouth 
and the intestines contain many varieties, while the stomach, 
on account of its acid contents, contains but few. The normal 
lungs are free from bacteria. 

The results of bacterial invasion are much influenced by the 
local conditions at the point of attack — the avenue of infection. 
These are of the greatest importance in determining the occur- 
rence or non-occurrence of infection. Certain bacteria, such 
as those of cholera, typhoid, and dysentery, attack only the 
intestinal canal, and will not cause trouble unless they first 
gain access to that tract. The gonococcus will not produce 
an infection in skin, even if that tissue be wounded. The 
tubercle bacillus in the lung can cause widespread destruction; 
in the skin little appears other than a localized tubercle. 

Of the various obstacles to infection, an intact epithelial 
covering of the body inside and out is probably the most im- 
portant. Such a covering is an efficient barrier against staphy- 
lococci and streptococci. An injury, nevertheless, need be but 
very slight in order to permit the organisms to enter. Such 
an injury may be secondary to the destructive action of prod- 



254 INFECTION 

ucts formed by the bacteria themselves. Associated infectioi 
may, likewise, be of importance. Tetanus organisms may not 
survive if inoculated alone into normal tissues, but will grow 
pyogenic bacteria are also present. The same probably holds 
good with the diphtheria bacillus. Both of these, although un- 
able to grow and multiply in an intact structure, can do so when 
these tissues have been previously or simultaneously bruised 
or lacerated. Although the epithelial coverings can protect, 
yet injuries to them are very common, and bacteria frequently 
gain entrance to the tissues. The question then arises, Why 
does not every infection become generalized and lead to the 
destruction of the host? There are two factors concerned in 
this problem. One is the aggressive or attacking force of the 
micro-organism, the other is the resistance which the host offers 
to the presence of the invader, to its multiplication, or to its 
ability to produce harmful substances. This resisting power is 
the defensive force. 

Aggressive Forces. — Certain bacteria, as those of diphtheria 
and tetanus, are possessed of a very low grade of infectious- 
ness, by which is meant their power of multiplying in the 
invaded body. The infection is almost always strictly local 
during the life of the individual; a general infection being ex- 
ceedingly rare, and occurring as a terminal or a postmortem 
condition. The tetanus bacillus, particularly, is practically 
unable to maintain itself in normal living tissues. In cases of 
infection it owes its limited development either to the damage 
done by an associated infecting agent or by direct mechanical 
injury. Even then the organism has frequently disappeared 
from the body entirely at the time when the patient is actually 
dying from the effects of its brief sojourn. Evidently, its 
aggressive powers are minimal and, even though it kills through 
its highly poisonous toxin, the resistance which the animal 
body offers to its presence is entirely sufficient to prevent its 
active development. Similar conditions exist in regard to the 
diphtheria bacillus. It is questionable whether it can gain 
access to the deeper tissues through intact superficial structures, 
but by means of its own toxin it is evidently capable of causing 
marked destruction after that superficial barrier has been 



TOXINS 255 

passed. The above instances show that the infectious and toxic 
properties of an organism are two independent factors, which 
in the case of tetanus and diphtheria bear an inverse relation 
to each other. 

An altogether different behavior is seen in a group of organ- 
isms represented by the anthrax bacillus and that of chicken- 
cholera. In these the local infection is followed almost im- 
mediately by a generalized infection, the organisms not only 
living, but actually multiplying freely in the body of the host. 
Their aggressivity, as compared with the previously mentioned 
type, is greatly developed, while their toxicity is practically 
nothing. 

Between these two types already mentioned stand the 
cholera vibrio and the typhoid bacillus. Their aggressivity is 
quite well developed, particularly that of the typhoid bacillus, 
which is commonly present in the blood and tissues. In addi- 
tion to their aggressiveness, the organisms of this class possess 
a well-marked toxicity, the effect of this appearing quite early 
in the course of the infection, and leading to a fairly char- 
acteristic clinical picture of the corresponding infectious dis- 
ease. 

Generally speaking, it may be said that the ability of micro- 
organisms to do harm depends upon the injurious nature of the 
substances they can produce. There are probably three groups 
of substances that are now recognized as of importance in con- 
nection with the clinical picture of the infectious diseases. 
They are: 

1. True toxins or exotoxins, extracellular and soluble. 

2. Endotoxins, intracellular and insoluble. 

3. Bacterial proteins. 

Toxins. — According to Ehrlich, the following are the char- 
acteristics of toxins: 

1. They are extremely easily destroyed (labile) substances 
which occur as secretion products of vegetable or of animal 
organisms. 

2. Their chemical nature is unknown. The impossibility 
of obtaining them in a pure form and their great lability render 
them insusceptible to ordinary chemical analysis. 



256 INFECTION 

3. An analysis of a toxin may be reached at present only 
through the medium of animal experiment. 

4. The introduction of toxins into the tissues causes the 
formation of an antitoxin with the production of immunity. 
It has not been possible to obtain antitoxins for inorganic poi- 
sons, as the alkaloids. 

5. In contradistinction to well-defined chemical poisons, the 
action of toxins is characterized by a latent or incubation period. 
The incubation period may be shortened experimentally by the 
injection of large quantities of toxin, but it cannot be elimin- 
ated entirely. Snake-venom, however, seems to act without 
an incubation period, but it is still to be classed with toxins 
because of its power to cause the formation of antitoxin. 

6. The facts make it necessary to assume as a condition for 
the poisonous action of toxins a specific union with the proto- 
plasm of the cells in certain organs. The affinity of other 
poisons, as alkaloids, for tissues depends not upon specific 
chemical union, but on some such process as solid solution or 
loose salt formation. 

The true toxins cause the physiologic and pathologic dis- 
turbances as a result of their solubility and the ease with which 
they can diffuse throughout the animal juices. The two chief 
toxin producers are the organisms of tetanus and diphtheria. 
A few of the tetanus bacilli may cause no local disturbance, yet 
may bring about the death of the individual. Toxins pro- 
duce specific symptoms ; consequently, it may be assumed that 
they have special selective affinities for certain tissues, and 
produce their symptoms in consequence of such affinity. This 
can be shown experimentally : a mixture of guinea-pig brain and 
tetanus toxin will prove harmless, although there may be 
present several times the fatal dose of the toxin. Other toxins, 
instead of being specific for the motor nerve-cells, may act upon 
the red blood-cells, or upon the leukocytes, or upon the cells of 
the respiratory centers, for instance. 

Endotoxins are insoluble substances not secreted by the living 
organism, but set free only after the death and disintegration of 
the parasites. They are not as specific in their action as the 
true toxins, but their injection into suitable animals gives rise 



CARDINAL CONDITIONS OF INFECTION 257 

to the production of antitoxins which are capable of neutraliz- 
ing the endotoxin employed. The toxic effect rapidly dimin- 
ishes on keeping, and is seriously impaired by exposure to higher 
temperatures — 55 to 6o° C. Many symptoms of disease 
may be due to the breaking down of the organism with the 
liberation of these bodies. 

Bacterial proteins constitute the main mass of the organ- 
ism. They differ from the toxins and endotoxins in not conform- 
ing to the characteristics of either of the two. Their effect is 
essentially pyogenic, the formation of pus, and is one common 
to most, if not all, bacteria. In some animals the pyogenic 
action does not manifest itself, because death results too early, 
but in more resistant individuals it can be shown. These 
proteins in themselves are not markedly dangerous, but they 
have gained in importance since it has been demonstrated that 
the introduction of foreign albumins leads not to increased 
resistance (immunity) against such proteins, but to hyper- 
sensitiveness (anaphylaxis). Consequently, a subsequent in- 
jection after a certain interval of time may produce serious 
symptoms or death. 

Ptomains are nitrogenous compounds of basic nature and 
alkaloid-like properties, formed from animal matter in con- 
sequence of bacterial decomposition. Their formation is 
only possible when special food stuffs are directly available, 
while toxin production is, within certain limits, independent of 
the food supply, and represents a specific function on the part 
of the micro-organisms in question. 

THE CARDINAL CONDITIONS OF INFECTION 

Infection can take place only when the micro-organisms are 
sufficiently virulent, when they enter in sufficient number, 
when they enter by appropriate avenues, and when the host is 
susceptible to their action. 

Virulence refers to the disease-producing power of micro- 
organisms which depends upon the invasiveness of the bac- 
teria, the toxicity of their products, or both. This property 
may vary greatly in different strains of the same variety of 
17 



258 INFECTION 

organism. Most bacteria when grown in artificial media will 
not be as virulent as those grown in some animal. If, however, 
animal fluids are added to the culture-media the virulence may 
be retained or even increased. In order to increase the viru- 
lence, the best results can be obtained by the transplantation 
of the organism from one animal to another without any inter- 
mediate growth on culture-media. This method, however, 
increases the virulence of the organism only for that particular 
kind of animal used. Transference through rabbits increases 
the virulence for rabbits, but not for other kinds of animals. 
This increase can continue to a certain point, beyond which it 
will not go. The number of organisms which is necessary to 
kill the animal becomes progressively smaller, and the period 
of incubation, the time between infection and the first symp- 
toms, shorter, until finally a strain is obtained in which the 
degree of virulence can no longer be increased by animal passage. 
This constitutes the "virus fixe." 

Number. — The number of bacteria gaining entrance has a 
very important bearing upon infection, and may determine 
whether it shall occur or not. When bacteria gain entrance 
into an animal there will always be some of the organisms that 
are unable to withstand the defensive powers of the host, 
and consequently perish. Others may be so weakened as to 
be unable to cause trouble, while some will be able to over- 
come the resistance, and give rise to disease. The more viru- 
lent the organism, the fewer will be the number required to 
infect. 

Avenue of Infection. — Local conditions are of the greatest 
importance in determining the occurrence or non-occurrence of 
infection. Cholera, typhoid, and dysentery attack the diges- 
tive tract alone. The gonococcus apparently can invade only 
through the mucous membranes of the genito-urinary apparatus 
or of the eye. The tubercle bacillus, although able to invade 
any tissue of the body, gives rise to modified forms of the dis- 
ease. If it invades the skin a local condition known as lupus 
occurs. This may last for years without becoming general. 
The same organism entering the lungs can give rise to con- 
sumption, with extreme destruction of tissue and generalized 



IMMUNITY 259 

infections. Skin infections in general tend to remain localized 
unless the organisms have been implanted quite deeply, so as to 
more readily gain access to the circulation. 

The chief obstacle to infection no doubt lies in the integrity 
of the epithelial coverings of the body, both inside and out. 
An injury, however, need be but very slight in order to allow 
the micro-organism to gain entrance. 

Susceptibility of the Host. — This varies greatly, some animals 
readily succumbing to infection by a certain organism, while 
other animals will be distinctly resistant. This resistance, 
however, may depend very largely upon the physical condition 
of the invaded individual. If anything occurs that will lower 
the general physiologic activity, the individual will then be 
less able to withstand the attack of the organisms. Fatigue 
is an apparent factor. When tired out, from one cause or 
another, infection is much more likely to occur. Exposure, 
particularly to cold, is a very common cause of lowering the 
bodily resistance, and thus allowing infection. Diet appears to 
have some obscure effect in predisposing to certain diseased 
conditions. Intoxication by poisonous substances increases 
the susceptibility to infection. This is quite commonly seen in 
the frequency and fatality of pneumonia among excessive in- 
dulgers in alcohol. Injuries of all sorts render the possibility 
of infection to become greater. 

When two different types of organisms invade the body at 
the same time the resulting condition is known as a mixed 
infection. 

If after one organism has caused tissue changes, another 
gains entrance and gives rise to pathologic conditions, it is 
called a secondary infection. 

IMMUNITY 

By immunity is meant the power to resist invasion by micro- 
organisms with the subsequent development of disease. An 
individual may be exposed to infection, but on account of some 
ability present may be able to resist and not acquire the disease. 

The lack of resisting power is known as susceptibility. 



260 INFECTION 

One form of immunity is the natural, in which there is an 
inherited resisting power that is common to certain races of men 
or of lower living beings. The second type is the acquired, in 
which the immunity has been obtained after birth, and may be 
either active or passive. 

Immunity is termed active when it results from the action of 
the cells within the invaded body, either in destroying the bac- 
teria or in neutralizing their injurious products. It is that 
form which follows an attack of an infectious disease and 
which lasts for a varying period. It may be very brief, as in 
cholera; for a longer time, as in typhoid; or sometimes for life, 
as in small-pox. It may be due to accidental infection; to the 
inoculation of a weakened virus, as in vaccination; to the intro- 
duction into the body of bacterial products without the micro- 
organism; or it may result from the inoculation of dead bac- 
teria, as in bacterination. 

Passive immunity is always acquired, never natural. It is 
that which is obtained by the introduction of the serum of an 
immunized animal into the body of a non-immune individual. 
The serum should always be introduced parenterally, that is, 
into the blood, subcutaneous tissues, or endothelial cavities, 
never by mouth, as it would then be acted upon by the digest- 
ive juices. It is supposed that in the serum of the first there is 
a substance that neutralizes the bacterial products in the blood 
of the infected animal. 

It must be remembered that immunity is a comparatively 
relative term. An animal may resist an ordinary dose, yet 
succumb if a very large amount, either of bacteria or toxin, be 
administered. The degree of immunity may be reduced by 
unhygienic surroundings, by fatigue, by exposure to abnormal 
temperatures, abnormalities of diet, drugs, pre-existing disease, 
and by injuries. 

Theories of Acquired Immunity. — i. Pasteur and Klebs be- 
lieved that the bacteria growing in the body used up some 
material that was necessary for their growth, and after dying 
left an unsuitable soil. This theory is not borne out by the 
facts. 

2. Wernich and Chaveau held that in the growth of bacteria 



THEORIES OF ACQUIRED IMMUNITY 261 

there were elaborated substances that inhibited their future 
development or activity. This theory also does not hold. 

3. The theory of phagocytosis. This is one of the most im- 
portant, and is strongly supported by many well-known in- 
vestigators. It, however, does not seem to be as satisfactory 
in general application as Ehrlich's "side-chain theory," which 
will be discussed later. 

There are certain cells in the body that have the power of 
ameboid motion, by means of which they are able to surround 




Fig. 99. — Phagocytosis: the Omentum Immediately after In^jection 

of Typhoid Bacilli into a Rabbit. 
Meshwork showing a macrophage, intermediate forms and a trailer, all con- 
taining intact bacilli (Buxton and Torrey). 

and take up bacteria and destroy them. These cells are known 
as phagocytes. Metchnikoff believes that immunity is the 
result of the positive and negative chemotaxis (power of at- 
traction) existing between phagocytic cells and micro-organisms. 
He divides such cells into two classes: 

(1) Micro phages — represented practically exclusively by the 
neutrophilic polymorphonuclear leukocytes. 

(2) Macrophages — large mononuclear leukocytes, endothelial 
cells lining serous membranes, and fixed mononuclear cells of the 
spleen follicles and lymph sinuses. 



262 



INFECTION 



The most active are the macrophages, as they have the power 
of independent motion. When the bacteria gain entrance into 
the body the phagocytes are attached, and they attempt to 




Fig. 100. Fig. ioi. 

Figs. 100 and ioi. — Cells with Various Receptors or Haptophorous 
Groups of the First Order. 
(a) Adapted to combination with the haptophorous groups (b) of vari- 
ous chemical compounds brought to them. It will be noted that there is 
no mechanism by which the toxophorous elements of the molecules (c) can 
be brought to the cell. 

ingest and destroy the invaders. If the immunity of the animal 
is marked, many of the organisms will be found within the cells; 
if the immunity is slight, few cells will contain bacteria. At one 





Mtw* 







Fig. 102. Fig. 103. 

Figs. 102 and 103. — Show the Regeneration of the Cell-haptophores 
or Receptors to Compensate for the Loss of Those Thrown Out 
of Service. 

time it was claimed that phagocytes could take up only dead 
bacteria, but it has been demonstrated that the leukocytes can 
take up living organisms. As a rule, the bacteria are ultimately 



THEORIES OF ACQUIRED IMMUNITY 



263 



destroyed, but on the other hand, the phagocyte may be the one 
to perish, and in this way permit a wide distribution of the 
invaders. Experiments have shown that the bacteria must be 
acted upon by a substance in the blood known as an opsonin, 
before the phagocyte is able to digest them. 

4. Ehrlich's lateral chain theory. This receives its name 
from its analogy to the benzole ring in chemistry with the 
accompanying lateral chains. For convenience terms are used 
that can be applied to formed bodies, although they cannot be 
demonstrated as such in the body juices. 



^ 



tf 



Xmto 




Fig. 104. — Shows the Number of 
Haptophores Regenerated 
by the Cell Becoming Ex- 
cessive, They are Thrown 
Off into the Tissue Juice. 



Fig. 105. — Explains What Anti- 
toxins are and How They 
are Formed. 

The liberated receptors in the 
tissue juice and in the blood possess 
identical combining affinities with 
those upon the cell , and meeting the 
adapted haptophorous elements in 
the blood, combine with them, thus 
keeping them from the cells. 



In this theory it is claimed that immunity depends upon 
the presence or absence of "receptors," the equivalent of the 
chemical lateral chains. The normal or fixed receptor is that 
body attached to the cell by means of which the cell is acted 
upon by various substances, nutritive or otherwise. Each 
receptor is supposed to be so formed as to unite with a certain 
body of a definite character. When the action of the bacteria 
upon the tissue cells is considered, it is supposed that the poison- 
ous products consist of two portions, the "haptophorous" and 



264 



INFECTION 



the "toxophorous" groups. The combination is thought to 
take place as follows: The haptophoric group unites with a 
certain definite receptor, and by so doing interferes with the 
normal function of the cell. At the same time the toxophoric 
group is able then to act directly upon the cell. If this group is 
very powerful the cell is destroyed, and if a sufficient number 
are involved the individual may die. When such a union 
occurs the receptors are of no further use. It has been found 
in such cases that in order to get back to the normal the cell 




Fig. 106. — Combination of Cell 
(a), Amboceptor (b), and Com- 
plement (c). 

The amboceptor may unite with 
the cell, but cannot affect it alone. 
The complement cannot unite with 
the cell except through the ambo- 
ceptor, having no adaptation to the 
cell directly. 




Fig. 107. 
Cell with receptors of the second 
order (a) by which the cells fix 
useful molecules, of albumins, etc., 
on one hand (b) , and zymogen mole- 
cules (c) on the other hand, and 
make use of the one substance 
through the action of the other. 



will be so stimulated that new receptors similar to the ones 
destroyed will be formed. As a rule, a great excess of receptors 
will result, and many of these will be cast forth into the circula- 
tion, becoming free receptors. These cast-off receptors are 
what constitute an antitoxin, and, on coming in contact with the 
toxin molecule, unite with the haptophorous portion and con- 
sequently render it harmless. It being attached to a free recep- 
tor, it is no longer able to combine with a fixed receptor. 
In bacteriolysis and hemolysis, or cytolysis in general, con- 



LYSINS 265 

ditions in which the destruction of actual cells is concerned, the 
destruction is brought about in a more complicated manner. 
Two other bodies than the cells are involved. One of these, 
known as the complement, is normally present in all serum. 
It is destroyed by a temperature of 55 C. for one-half hour, 
and is termed, therefore, thermolabile. The other, the immune 
body, or amboceptor, occurs in serum only as the result of the 
injection into the individual of the definite antigen. In other 
words, the amboceptor is specific in that it can combine only 
with that substance which gave rise to its formation. As it 
can resist heat up to 8o° C, it is termed thermostabile. In 
order that the cell be destroyed the complement unites with the 
specific amboceptor, which in turn joins with the fixed receptor, 
and the destructive action then occurs. 

In active acquired immunity against foreign cells the in- 
vaded animal forms large amounts of amboceptor, which, being 
free within the blood, unite with and destroy the invading cells. 
If the supply is sufficient, the individual will recover. In 
passive acquired immunity large numbers of amboceptors 
in the serum from the immunized animal are directly intro- 
duced into the patient, and in this way effect a cure. 

Lysins are those antibodies that will cause the destruction 
of cells, and they receive various names, according to the type 
of cell acted upon. The destruction is known as lysis. Cyto- 
lysin is the general name of all the substances that destroy 
the cells. A bacteriolysin causes lysis of bacteria; a hemolysin, 
that of erythrocytes. 

It has been found, for example, that a "hemolysin" can be 
produced by injecting defibrinated rabbit's blood into a guinea- 
pig. The serum of the guinea-pig will develop marked ability 
to dissolve blood-corpuscles from the rabbit. This action 
can be destroyed by heating the serum to 56 C, but the serum 
can be reactivated by the addition of fresh normal serum, as 
in it will be found complement. The immune serum will con- 
tain the amboceptor or immune body. 

A. Foreign cells, blood, bacteria, etc. 

B. Teated immune serum containing amboceptor, but no 
complement, 



266 INFECTION 

C. Unheated normal serum containing complement, but no 
amboceptor. 



B = No lysis. 



A + C = No lysis. 



A + B -f C = Lysis. 



A^ 




A >< C 



^MKJD 



Fig. 108. — Diagram Representing Method of Combination oe 
Antigen (A), Amboceptor (B), and Complement (C) in Producing 
Lysis. 

In order to bring about the solution the three factors must 
be present. Experiments show that the complement cannot 
combine directly with the cell, but that there must be an inter- 
mediate substance, which is known as the amboceptor. 

Agglutinins. — When bacteria or other cells are injected into 
the body there are formed within the serum definite substances, 
which when brought together with emulsions of the correspond- 
ing bacteria will cause the "clumping" or agglutination of the 
bacteria. If these are normally motile they will become less 
motile, and may lose that power entirely. 

As the action is specific, it is commonly used for diagnostic 
purposes, especially in typhoid fever, when it is known as the 
"Widal reaction" (q. v.). 

Precipitins. — It has been found that when an immune serum 
is brought together with a clear filtrate of a bouillon culture of 
the organism used for injection, there will appear a turbidity 
which will collect gradually at the bottom of the test-tube as a 
precipitate. 

Such substances are formed whenever foreign albumins, 
either of vegetable or animal origin, are introduced through 
parenteral channels. These bodies are called precipitins. 

These precipitins are specific in their reaction, and have 
been used for the purpose of identifying the origin of various 



ANAPHYLAXIS 267 

albumins. Under the term of the "biologic" blood- test this 
action has been employed in medicolegal cases to determine 
the source of blood-stains. It is also made use of in establish- 
ing zoologic relationships between different animals. 

If human blood is injected a number of times into a rabbit, 
the serum from the rabbit's blood will form a precipitate with 
normal human blood-serum when the two are mixed in a test- 
tube. 

It is thought by some that the agglutinins and precipitins 
are practically similar substances; agglutination being a bring- 
ing together of cell; precipitin action, the bringing together of 
albuminous particles. 

Anaphylaxis is a term applied to an increase of susceptibility 
to infection; it is the opposite of prophylaxis. It is a reaction 
that will occur with the parenteral form of injection of foreign 
proteins of any kind. In order to obtain the characteristic reac- 
tion it is necessary that a period of from six to ten days inter- 
vene between the first and second injection. A guinea-pig may 
be sensitized by 0.001 gm. of horse serum introduced into the 
peritoneal cavity. Eight to ten days later a second injection 
of 0.1 gm. of the serum is given, at which time the animal will 
become restless, short of breath, scratch itself violently about 
the nose, then depressed, and dies within one hour. Autopsy 
shows the lungs to be greatly distended and numerous small 
hemorrhages present. Similar symptoms have been encoun- 
tered in people who have received antitoxin horse serum. In 
addition, there are skin eruptions, joint-pains, and edema, a 
condition known as serum sickness. 

The anaphylactic reaction is specific, and the susceptibility, 
once acquired, may continue throughout the life of the animal, 
and may be transmitted by the blood of the mother to the 
offspring. It may be natural or acquired, active or passive. 
It may also be general or local. 

The possibility of local anaphylactic reactions has been made 
use of in the diagnosis of various diseases, particularly tuber- 
culosis. The subcutaneous injection of tuberculin in a non- 
tuberculous person will cause no disturbance. The same dose 
in the tuberculous will cause headache, muscle pains, fever, 



268 INFECTION 

and local reddening around the site of inoculation. Similar 
results are obtained if the tuberculin is instilled in the eye 
(Calmette reaction), but as severe inflammations have been 
occasioned, the method is not recommended. A like reaction 
is claimed when luetin, a specially ground-up culture of the 
Treponema pallidum, is employed as a subcutaneous reaction 
for syphilis. Much experimentation is being done along this 
line in respect to the making of diagnoses in various diseases. 
The symptoms of many diseases may be due to the presence 
of foreign proteins that have sensitized the individual. 

According to Vaughan, anaphylaxis results when the strange 
protein in the blood reaches the cells and is slowly broken down 
by enzymic action. The cells, having once acquired the prop- 
erty of destruction, seize eagerly upon the protein the next time 
it is offered, disintegrate it rapidly, and so disseminate through- 
out the body the disintegration products, some of which may 
be toxic and account for the reaction. 

Complement Fixation. — The well-known Wassermann test 
for syphilis is nothing more than the application of the com- 
plement-fixation reaction to diagnostic purposes. It is a 
method of making the diagnosis of syphilis by demonstrat- 
ing in the blood (or cerebrospinal fluid, milk, or urine) of the 
patient a complement-fixing substance not present in normal 
blood. 

The test is twofold: (i) A combination of syphilitic antigen, 
complement, and suspected serum. (2) A subsequent addition 
to the mixture of blood-corpiiscles and hemolytic amboceptor. 
If the suspected serum contain the syphilitic antibody, the 
antigen and the complement unite with it, and the complement 
being thus "fixed," no hemolysis can take place upon the sub- 
sequent addition of the blood-corpuscles and hemolytic serum. 
If, on the other hand, the suspected serum contain no antibody, 
the complement cannot be fixed, and is, therefore, free to act 
upon the subsequently added blood-corpuscles in the presence 
of the hemolytic serum, and hemolysis results. 

It is thus seen that the first test is made for the purpose of 
fixing the complement, and the second for the purpose of finding 
out whether or not it has been fixed. 



COMPLEMENT FIXATION 269 

The materials required for the Wassermann test are as follows : 

A. Fresh sheep red blood-cells that have been thoroughly 
washed so as to get rid of any complement. 

B. Blood-serum from a rabbit that has been immunized 
against the blood-cells of a sheep. 

C. Immunized rabbit serum (B) that has been heated to 
56 C. for thirty minutes in order to destroy the complement, 
but not affecting the specific amboceptor or immune body 
which can resist such a temperature. 

D. Normal serum from a guinea-pig containing complement. 

E. Antigen. Extract of the liver of a syphilitic fetus in 
alcohol, ether, or water; or lecithin, cholesterin, or extracts from 
organs of non-syphilitics. 

F. Fluid suspected to contain syphilitic antibody (ambocep- 
tor). This should be heated to 56 C. for one-half hour to 
destroy the complement. 

For the actual performing of the test there are also needed — 

E 1. Serum from a known case of syphilis, containing, there- 
fore, the syphilitic amboceptor. This also must be heated. 

E 2. Serum from a known non-syphilitic* 

Before using the solutions in the hemolytic series (C and D) 
they must be carefully standardized, so as to determine just 
what amount of amboceptor and of complement are necessary 
in order to cause hemolysis exactly. Such an amount is called 
a unit. 

D, complement 

+ 

E, syphilitic antigen 
+ 

F, suspected fluid 



Incubated for one | A, sheep corpuscles 

hour at 37 C. <{ + 
Then add C, hemolytic amboceptor. 



The combination of the two systems is placed in an incubator 
at 37 C. for one hour, then put in the ice-box for twenty-four 
hours, at the end of which time the final conclusions are drawn. 

If F contains the syphilitic amboceptor, it will combine with 
both D, complement, and E, the syphilitic antigen. Conse- 
quently, when A and C of the hemolytic system are added, it 
will be found that the complement D has been already used 
or fixed. Therefore no free complement is present to unite 



270 INFECTION 

with A and C and cause hemolysis. A positive Wassertnann is 
indicated by the absence of hemolysis. 

If F does not contain syphilitic amboceptor the complement 
D will remain free, and when A and C are added, it will combine 
and cause the destruction (hemolysis) of the sheep corpuscles (A) . 
A negative Wassermann, therefore, is indicated by the presence of 
hemolysis. 

When there is no hemolysis the blood-cells will be in the 
bottom of the test-tube, and the liquid will be clear and color- 
less. In hemolysis there may be either a complete or a partial 
destruction of the red cells, and the overlying fluid will be of a 
reddish color, the degree depending upon the amount of cellu- 
lar disintegration. 

E 1 and E 2 are employed as controls in the series of tests 
necessary to determine the accuracy of the solutions that are 
used in the reactions above mentioned. 

A positive Wassermann is nearly conclusive of there being a 
syphilitic infection. In active syphilis positive reactions have 
occurred in as much as 94 per cent, of the cases; in latent 
syphilis, 50 per cent.; and in chronic diseases of the nervous 
system, as general paresis and tabes dorsalis, the figures vary 
from 90 per cent, in the first to 50 per cent, in the latter. 

On the other hand, a negative Wassermann does not exclude 
syphilis, as the result may be due to the treatment; as under 
active treatment with mercury and the iodids, salvarsan, or 
neosalvarsan the reaction is usually negative. 

Antitoxin Manufacture. — As has been stated, if small doses of 
some special poison, such as diphtheria toxin, be repeatedly 
injected into a susceptible animal in increasing amount there 
will be developed in the blood-serum of that animal an antibody, 
called an antitoxin. This is formed by the cells and, according 
to Ehrlich's side-chain theory, corresponds to the free receptors. 
By injecting the antitoxin into an immunized animal it can 
resist a dose of toxin that ordinarily would be several times more 
than necessary to kill. That a combination occurs between the 
toxin and antitoxin can be proved by mixing the two together 
in a test-tube. The resulting mixture will prove harmless when 
injected into a susceptible animal. 



PREPARATION OF DIPHTHERIA ANTITOXIN 271 

Antitoxins are destroyed by heat, acids, and many chemicals, 
and gradually deteriorate spontaneously when in solution, 
particularly when kept at room-temperature. To preserve their 
activity the temperature should be not more than 5 C. Anti- 
toxins are specific in that they neutralize the corresponding 
toxin and have no other apparent action within the body. 
The occasional ill effects, such as serum sickness, following the 
injection of antitoxic serums are due to other substances (the 
proteins in the serum) and not to the antitoxins themselves. 
Antitoxins may be injected subcutaneously, intravenously, into 
the subarachnoid space, into a nerve, into the brain substance, 
or into any of the body cavities. They are practically useless 
when given by the mouth, as very little is absorbed. As anti- 
toxins, when injected into an organism, tend to disappear rather 
quickly, passive or antitoxic immunity is, therefore, transient; 
it cannot be depended upon for more than ten days or two weeks. 
When antitoxic serum is injected subcutaneously the antitoxin 
is absorbed slowly, requiring about forty-eight hours before it 
appears in the blood in maximum amount. When very prompt 
action is necessary the antitoxin should be introduced directly 
into the circulation by intravenous injection. Antitoxins are 
valuable both as curative and immunizing agents. For curative 
purposes they should be given early and in large enough doses 
to get their action before damage has been done by the toxins. 

Preparation of Diphtheria Antitoxin. — As similar methods are 
used for practically all types of toxins, a description of the 
preparation of diphtheria antitoxin will be sufficient. 

To obtain the necessary toxin virulent diphtheria bacilli 
are grown in alkaline bouillon containing 0.2 per cent, dextrose 
at a temperature of 37 C. for five to seven days. The bouillon 
culture is then passed through a porcelain or Berkefeld filter 
and stored in sterile containers in an ice-box. On account 
of general convenience horses are commonly employed. They 
should be perfectly healthy, free from glanders, tuberculosis, or 
tetanus. The horse is injected hypodermically with 0.1 c.c. 
of the toxic filtrate. This is frequently followed by a rise in tem- 
perature, local reaction, and some general disturbance. When 
these disappear, a second dose is given. The doses are cautiously 



272 INFECTION 

increased in amount and administered every few days until 
from 500 to 1060 c.c. of the toxin can be given without effect. 
When the degree of immunity is sufficiently high, blood is drawn 
from the jugular vein to the amount of from 3 to 9 liters, accord- 
ing to the size of the horse, collected in sterile bottles, then 
placed on ice for several days until the clear serum separates 
from the clot. This is then drawn off from the coagulated 
blood under aseptic precautions, and in it is the antitoxin. It 
is preserved by the addition of small amounts of phenol, trikresol, 
etc.; this latter seems to be the most satisfactory. After the 
serum has been obtained, its strength or potency, as expressed 
by the term immunizing units," must be determined. An anti- 
toxic unit may be defined as being ten times the least quantity 
of antitoxic serum that will protect a standard (300-gra.) guinea- 
pig against ten times the least certainly fatal dose of toxic bouillon. 

To determine the strength of any given serum, the minimum 
fatal dose of a sterile toxin for a 300-gm. guinea-pig must be 
ascertained. Then must be determined the least quantity of 
antitoxic serum that will protect a guinea-pig against ten times 
the ascertained minimum fatal dose of the toxin. The neces- 
sary dose of antitoxic serum is expressed as a fraction of a cubic 
centimeter and multiplied by 10, the result equaling one unit. 

Ehrlich, in determining the unit, makes use of a standard 
antitoxin (antitoxins not deteriorating or varying as do toxins) 
by which the antitoxin combining power of the test toxic bouillon 
is first determined. The toxin unit (the smallest amount of toxin 
required to kill a guinea-pig weighing 300 gm) having been found, 
is then used to determine the antitoxic unit of antitoxins of 
unknown strength. 

The power of antitoxic serums differ greatly: some contain 
200 to 300 units per cubic centimeter, while others may contain 
even 1700 to 2000 per cubic centimeter. 

Inasmuch as the antitoxin is only a small portion of the 
serum, various methods have been sought, by means of which 
the useless, and sometimes harmful, portions may be eliminated. 
The method employed at present in order to obtain such a con- 
centrated antitoxin is that elaborated by Gibson — that of 
globulin precipitation. 



BACTERIN ATION 273 

Tetanus Antitoxin. — The method of obtaining is similar to 
that employed for securing the diphtheria antitoxin, the unit, 
however, being somewhat different. The use of this antitoxin 
has not been as satisfactory as that of diphtheria, on account of 
the rapidity with which the central nerve-cells combine with the 
tetanus toxin and the firmness of that union. Consequently, 
as a curative after toxic symptoms have developed, it is not very 
efficient, although more cases of tetanus do recover after anti- 
toxin treatment than after any other form. Its chief value is as 
a preventive. It should be given as soon as possible after the 
injury has been received, in order that the free receptors will be 
present ready to combine with the toxin as soon as it has formed. 
By means of this prophylactic dose of antitoxin the number of 
fatal cases of tetanus infection following injuries received on the 
4th of July has decreased very greatly. 

Bacterination (bacterial vaccine) refers to the introduction 
within the body of measured amounts of sterile cultures of 
bacteria, in order that the individual may develop an im- 
munity to that particular organism. This method has been 
employed in the infections of many varieties of bacteria, with 
particularly favorable results where the cocci have been the in- 
vaders. In pyorrhea alveolaris much success has been attained. 

Two types of bacterins (vaccines) are employed, the stock 
vaccine and the autogenous vaccine. In the latter the bac- 
terin is obtained by the cultivation of the organisms present in 
the lesion of the infected person. The stock vaccine is made of 
bacteria similar to those in the infected individual, but obtained 
from some other source. As a rule, better results are obtained 
by using the autogenous cultures, although in gonococcal infec- 
tions the stock bacterin seems to be more satisfactory in many 
instances. 

Preparation of a Bacterin. — The vaccine is usually prepared 
from a fresh twenty-four-hour growth of a pure culture of the 
micro-organism on an agar slant. The growth is scraped off 
and made into an emulsion with physiologic salt solution. The 
emulsion is then sterilized by heating at 6o° C. for one hour 
and afterward is further diluted. This is done so that 1 c.c. 
will represent approximately the dose to be given. This dilu- 



274 INFECTION 

tion will vary, as the number of bacteria to a dose varies accord- 
ing to the organism used. Culture-tubes are inoculated with the 
vaccine and incubated for twenty-four hours at 37 ° C. to make 
sure that the sterilization was complete. To preserve the 
bacterin, 0.5 per cent, of carbolic acid or trikresol is used. 

The injections should always be given subcutaneously. 
Usually three or four injections are given at intervals of from 
five to ten days, as in this way an immunity of much higher 
grade and longer duration is obtained. In most instances the 
acquired immunity lasts from two to five years and may be 
renewed. 

Preventive inoculations with bacterial vaccines have been 
used extensively against typhoid fever, plague, and cholera. 

The bacterins are used also as curative agents, but much 
care should be observed in giving the proper dosage. A mini- 
mum amount should be given, and if it creates no unfavorable 
reaction, a larger amount should be given subsequently. 

Opsonins. — It has been shown that in the serum of persons 
convalescent from infectious diseases or vaccinated (by bac- 
terins) against certain infectious diseases substances are present 
which prepare the micro-organisms for the action of the phago- 
cytes. These substances are termed opsonins. If fresh blood 
is mixed with an emulsion of some bacteria, and then incubated 
for one-half hour, it will be found that many of the bacteria are 
within the polymorphonuclear leukocytes. If the serum is 
washed away from the leukocytes before adding the bacteria, 
none of the latter will be found within the leukocytes. In order 
to show that this effect is on the bacteria rather than on the 
leukocytes, the bacterial suspension may be treated with some 
serum for one-half hour, then washed free from this serum by 
means of salt solution and a centrifuge, and then mixed with 
some serum-free leukocytes; then it will be found that phago- 
cytosis occurred as before. 

The estimation of the opsonic power of the serum has been 
attempted and various methods elaborated. It may be ques- 
tioned, however, whether any of the tests now in use is a true 
index of the amount of opsonins in the serum, although it may 
be taken to indicate roughly the measure of their activity. 



CHAPTER XVI 

LABORATORY TECHNIC 

EXAMINATION OF FRESH MATERIAL 

The examination of fresh material may be made by teasing 
the tissue in water or, preferably, 0.6 per cent, saline solution. 
This, however, may not be satisfactory unless the tissue has 
been allowed to remain in some fluid long enough for the cells 
to become separated from the basement membrane. This 
is known as maceration; the following fluids are used for this 
purpose : 

1. Alcohol, 33 per cent. (Ranvier), in which soak the speci- 
men twenty-four hours. 

2. Very weak chromic acid solutions, 1: 10,000, or its salts. 
Muller's fluid is especially useful for nervous tissue. Leave 
in the acid twenty-four hours; in the latter, three to five days. 

3. Osmic acid, 1 per cent., for twelve to twenty-four hours. 
Is useful if there is any fat present. 

4. Potassium hydrate, ^ per cent., for from fifteen to twenty 
minutes. The specimen should be examined in the same fluid, 
as water distorts the cells. To preserve the tissue, wash in 50 
per cent, acetic acid, then in water, and after staining in alum 
carmin can be mounted in glycerin. Is good for the examina- 
tion of tissues or tumors that contain smooth, involuntary 
muscle-fibers. 

5. Arnold's method: The small pieces of tissue are placed 
for five to ten minutes in 1 per cent, acetic acid, then for twenty- 
four to forty-eight hours in the weak chromic acid solution. 
They may finally be stained with picrocarmin. 

Various reagents may be used in the examination of fresh 
specimens to render them transparent, to bring out certain 
details, or to cause various substances to disappear: 

275 



276 LABORATORY TECHNIC 

i. Glycerin clears the tissues and has the advantage of not 
changing chemically nor getting thin. Permanent mounts 
may be made by sealing the edges of the cover-glass with 
paraffin. 

2. Potassium acetate in a saturated watery (50 per cent.) 
solution has a clearing action similar to, but less marked than, 
glycerin. 

3. Acetic acid: Has the advantage that it causes the nucleus 
to shrink and the connective tissue to swell and become trans- 
parent. It does not affect fat, but dissolves the protein granules, 
so differentiates the two processes. Elastic fibers and micro- 
organisms are unaffected, so stand out prominently against 
the changed connective tissue. The acid may also be used to 
dissolve calcium salts. Solutions of 1 to 2 per cent, are generally 
employed, but the pure glacial acetic acid may be used. 

A solution of acetic acid with fuchsin may be employed and 
in that way stain the nuclei. 

4. Weak watery solutions of iodin. The following solution 
(Lugol's) is mixed with 3 to 5 parts of water: 

Iodin 1 

Potassium iodid 1 

Distilled water 100 

This brings the nucleus and the cell contour more plainly 
to view and also stains glycogen and amyloid particles brown. 

5. Potassium and sodium hydrate solutions of from 1 to 3 
per cent, have the power to dissolve most tissues, but do not 
affect elastic tissue, fat, bone, pigment, bacteria, or amyloid. 
Thirty-three per cent, solutions dissolve the cement substance 
and isolate the cells. This reaction takes place in a few min- 
utes. 

6. Osmic acid in 1 per cent, watery solution will stain fat 
black or brown. 

7. Hydrochloric acid in from 3 to 5 per cent, is used for the 
recognition of lime salts, either in bone or in the tissues which 
it dissolves, with the production of bubbles of C0 2 . 

8. Fresh preparations may be stained by allowing a few 
drops of watery stains to pass under the cover-glass and then 



FORMALIN 277 

washing out the excess. Methyl-green, Loffler's methylene- 
blue, or acetic acid fuchsin may be used. Hematoxylin is 
unsuitable. 

FIXATION AND HARDENING 

If a more exact examination is desired, the tissues must 
be hardened and fixed. The material should be placed in the 
fluid used as soon as possible after it has been obtained. The 
point desired is that the conditions as they exist in the tissues 
during life shall be retained. 

The different solutions vary greatly in their power of pene- 
tration and also in their effects upon different tissues. The 
action is facilitated by cutting the specimen in small pieces. 
After fixing and hardening it is generally necessary to thor- 
oughly wash, so as to remove all traces of the agent employed. 

The points to be observed are: 

The specimens should not be more than 2 mm. in thickness. 

The volume of reagent used should be from ten to fifteen 
times larger than the bulk of the specimen. 

Place a layer of absorbent cotton or filter-paper in the bot- 
tom of the jar, so that the tissue may be acted upon by the 
fluid from all sides. 

After sufficient hardening, remove the specimen and wash 
it in running water for twelve to twenty-four hours. It is 
then passed through alcohols of various strengths — 70, 80, 
and 90 per cent., about twenty-four hours in each. 

1. Alcohol. — It is used for rapid work and particularly if 
bacteria are suspected. It is not good for nervous tissue. 
Specimens should, as a rule, be put in weaker alcohol before 
being placed in absolute. This method is not used as much 
as formerly, on account of the shrinking and distortion of the 
tissues and the destruction of the red blood-corpuscles. 

The so-called absolute alcohol is usually little more than 
95 per cent. To extract the water, copper sulphate should 
be heated until the blue color disappears and then added to the 
alcohol. The alcohol should be filtered before using and the 
copper sulphate reheated when it begins to turn blue. 

2. Formalin. — This reagent is being used very greatly in 



278 LABORATORY TECHNIC 






place of alcohol. It has numerous advantages. The hardening 
takes place rapidly, the erythrocytes and other pigments retain 
their natural colors. 

As formalin is bought it consists of a 40 per cent, solution 
of formaldehyd in water. The strength commonly used is 
a 1 : 10 or a 4 per cent, solution. 

The tissues are left from four to six hours in the 4 per cent, 
solution, then thoroughly washed in water, and finally passed 
through alcoholic solutions of varying strengths. 

Formalin is also used in combination with other mixtures, 
particularly as Orth's solution. This is made by adding 10 
parts of formalin to 100 parts of Mutter's fluid. This should 
be made fresh, as in the course of five or six days there is a crys- 
talline precipitate formed. This fixes nuclear figures very well 
and hardens small pieces of tissue in from three to six hours. 
It is particularly important that they should be very carefully 
washed in running water. Is good for nervous tissues. 

3. Muller's fluid is made up of: 

Potassium bichromate : 2.5 

Sodium sulphate 1.0 

Distilled water 100.0 

This should be used in large quantities and should be changed 
every second day for about five times, and then be replaced 
whenever the solution becomes cloudy. To prevent the growth 
of mold 1 gm. of bichlorid of mercury should be added to 2 liters 
of the fluid. 

For thorough hardening of small objects from ten to twelve 
weeks is required; for a large object, like the brain, a year. 
The process can be hastened by placing the preparation in an 
incubator and frequently changing the fluid. 

After complete hardening the preparation is carefully washed 
in water, and then run through increasing strengths of alcohol. 
The sections stain well with hematoxylin and eosin. The red 
corpuscles are well preserved. 

4. Erlicki's fluid consists of: 

Potassium bichromate 2.5 

Sulphate of copper 0.5 

Distilled water 100.0 



OSMIC ACID 279 

This fluid has the advantage that preparations will harden 
in from eight to ten days; and if in the incubator, in fiom 
four to five days. Its disadvantages over Mliller's fluid are 
that it does not prevent shrinking as well and that there is 
frequently a precipitate in the tissues. 

5. Bichlorid of mercury is of particular value in the fixation 
of cells and mitotic figures, but it has very little penetrating 
power. All the solutions that contain bichlorid have the 
drawback that there is a precipitation of mercury in the tissues 
that may be mistaken for pigment unless removed. These 
compounds may be dissolved by the addition of several drops 
of iodin to the 80 per cent, alcohol into which the specimens are 
put after having been washed. The iodin may be added to the 
alcohol in which the cut specimens are placed before being 
stained. 

6. Zenker's Fluid. — 

Bichlorid of mercury 5.0 

Potassium bichromate 2.5 

Sodium sulphate 1.0 

Distilled water 100.0 

Glacial acetic acid 5.0 

The mercury and bichromate are dissolved in warm water 
and the sodium then added. It is best not to add the glacial 
acetic acid until the solution is ready to be used, as the acid 
rapidly evaporates. 

After being in the fluid for twenty-four hours or less, accord- 
ing to the size of the specimen, it is thoroughly washed in 
running water twelve to twenty-four hours and then hardened 
in alcohol. The tissue should be passed through 80 per cent, 
alcohol containing iodin so as to remove the precipitate of 
mercury that forms. 

Tissues prepared in this way stain according to all methods. 
The chromatin figures are well preserved as well as the erythro- 
cytes. 

7. Osmic Acid. — Its penetrating power is very slight, so very 
thin pieces of tissue, not more than 5 mm. in thickness, can be 
used. 



280 LABORATORY TECHNIC 

A i per cent, watery solution is usually employed. It 
should be kept in the dark, and when the specimen is fixed, 
well washed. The paraffin method of embedding should be 
employed, using chloroform or clove oil, as the celloidin will 
dissolve out the fat. In clearing, do not use xylol, as it also 
dissolves fat. 

8. Flemming's Solution. — 

Aqueous chromic acid solution (i per cent.) 15 

Aqueous osmic acid solution (2 per cent.) 4 

Glacial acetic acid 1 

The small bits of tissue are left in the fluid one to three days, 
well washed for several hours, then hardened in increasing 
strengths of alcohol. It is used for karyokinetic figures and for 
fat. Stains best with watery safranin. 

9. Hermann's fluid is a modification of the above. A 1 per 
cent, platinum chlorid solution is used instead of the chromic 
acid. The nuclear figures are especially well preserved. The 
method of employment is the same as with Flemming's. 



DECALCIFICATION 

General Rules. — The tissue must be well hardened before 
being put in the decalcifying fluid, otherwise it will be much 
altered. The formalin method is well adapted and small pieces 
should be used. 

An excess of fluid should be used and it should be frequently 
changed. After complete decalcification the tissue should be 
carefully washed for two or more days. It must then be 
rehardened before it is ready to cut. The tissue is decalcified 
if it allows a needle to penetrate without meeting distinct 
resistance. 

The following are the fluids commonly used: 

1. Chromic Acid and Its Salts. — Miiller's fluid for small 
pieces of bones or embryonal bones. It is a very slow process. 
Can be hurried by placing in an incubator. 

2. Saturated Watery Solution of Picric Acid. — Requires 
about three weeks for embryonal bones. Larger and older 



PHLOROGLUCIN 251 

pieces take several months. Can be hastened by adding 
3 to 5 per cent, of nitric acid. To remove the picric acid, wash 
the tissue, then place in 95 per cent, alcohol to which several 
drops of a saturated watery solution of lithium carbonate have 
been added. The fluid becomes colored and more carbonate 
should be added until it remains completely clear. 

3. Hydrochloric Acid. — When used in 1 to 10 per cent, solu- 
tion it works quite rapidly, but injures the tissues. Is best 
used as: 

Ebner's fluid: 

Hydrochloric acid 2.5 

Alcohol 500.0 

Distilled water 100.0 

Sodium chlorid 2.5 

This method can be hastened by increasing both the hydro- 
chloric acid and sodium chlorid to 5 per cent. 

4. Nitric acid, in from 3 to 10 per cent, in water or formalin, 
is well adapted for bone tissue from adults. The alteration to 
the tissue is less than when corresponding solutions of hydro- 
chloric acid are used. 

Haug recommends the following on account of its more 
rapid and better action: 

Nitric acid, c. p 30.0-90.0 

Absolute alcohol 700.0 

Distilled water 300.0 

Sodium chlorid 2.5 

5. Phloroglucin. — This protects the tissues from the action 
of the acid, so that very strong solutions may be used. It acts 
very rapidly: small pieces are decalcified in one-half hour; 
larger ones, in several hours. 

A stock solution is made consisting of: 

Nitric acid, c. p 10 c.c. 

Phloroglucin 1 gm. 

This is carefully dissolved by warming; is best done under 
a hood. To this is added 100 c.c. of a 10 per cent, aqueous 
solution of nitric acid. 



282 LABORATORY TECHNIC 

A more slowly working mixture is: 

Phloroglucin 1 

Nitric acid 5 

Alcohol 70 

Distilled water 30 

Thotna's method is to: 

1. Harden in Miiller's fluid or alcohol. 

2. Decalcify in: 

Alcohol 5 

Nitric acid 1 

changing the solution very frequently. 

3. Wash in alcohol. 

4. Wash thoroughly in alcohol to which has been added 

an excess of calcium carbonate. 

The decalcification requires from two to three weeks for 
large pieces. To remove the acid the tissue has to be in the 
carbonated alcohol from eight to fourteen days; should remain 
until there is no acid reaction with litmus-paper. 

6. Trichloracetic acid, used in 5 per cent, aqueous solution 
and frequently changed, decalcifies in from five to seven days; 
generally with good results. 

INJECTION 

For the purpose of making them more easily studied the 
blood-vessels and other hollow structures may be filled with 
some injecting material that contains a stain. This pro- 
cedure is not frequently used for pathologic purposes. 

EMBEDDING METHODS 

The purpose of embedding is to give to a tissue a sufficient 
firmness to permit the cutting of thin sections. Two methods 
are commonly employed — one with celloidin, the other with 
paraffin. 

Celloidin has the advantage of not requiring heat, and can 
be used for larger pieces of tissue. On the evaporation of the 
alcohol and ether a comparatively solid mass remains. 



CELLOIDIN METHOD 283 

Paraffin can be used for small pieces of tissue only. It 
also renders the specimen brittle, so that it is frequently diffi- 
cult to cut good sections. Although fluid when kept at the neces- 
sary heat, the paraffin becomes hard on cooling. 

Celloidin Method. — In this process two solutions of celloidin 
of different thicknesses are employed — one of the consistency 
of syrup, the other of that of molasses. These solutions are 
made by adding to a mixture of equal parts of absolute alcohol 
and ether enough celloidin to give the desired consistency. 
The specimens must be thoroughly dehydrated in absolute 
alcohol and then placed in equal parts of absolute alcohol and 
ether for twenty-four to forty-eight hours. This latter step is 
not essential, but is advisable. From the alcohol the specimens 
are left in the thin celloidin at least twenty-four hours and in 
thick celloidin for a like period. If there is no hurry, the longer 
the time in each celloidin solution, the better will be the result. 
They are then placed on blocks, covered with thick celloidin, 
and allowed to harden. In the course of a few minutes, when 
the block can be turned upside down without the specimen 
sliding off, they should be placed in 80 per cent, alcohol. After 
remaining there for several hours they are ready to cut. 

The blocks best adapted for use are those made out of vulcan- 
ite or hard paraffin. The latter are particularly convenient. 
A square of hard paraffin is cut up into blocks of various sizes 
and the tops roughened with a knife so as to give a better surface 
for the celloidin to adhere to. Cork and wood are not well 
adapted, as after being in the alcohol for any length of time the 
tannic acid is extracted; it penetrates the specimen and inter- 
feres with its staining properties. 

In cutting celloidin sections the knife is clamped at a very 
marked slant, so that as much of it as is possible will be used. 
The blade and the specimen should be kept constantly wet 
with 80 per cent, alcohol. As the sections are cut they are 
lifted off the knife with a camel's-hair brush and placed in a 
dish containing water. This causes them to flatten out. 

After the staining has been completed the sections are passed 
through graded alcohols to remove the water and are then 
placed in some fluid that will clear them. Clove oil should 



284 LABORATORY TECHNIC 

not be used, as it dissolves the celloidin. Bergamot, cedar oil, 
creosote, and xylol, alone or in combination with 1 part of car- 
bolic to 3 parts of xylol, do not affect the celloidin. 
Summary : 

1. Dehydration in absolute alcohol. 

2. Absolute alcohol and ether, equal parts, one to three days. 

3. Thin celloidin, one to five days. 

4. Thick celloidin, one to five days. 

5. Mount on block. 

6. Alcohol (80 per cent.), twelve to twenty-four hours. 

7. Cut on microtome. 

8. Stain, dehydrate, and clear. 

9. Mount in balsam. 

Paraffin Method. — The preparation must be thoroughly 
dehydrated in absolute alcohol or anilin oil. It is then placed 
in some fluid that is a solvent of paraffin — xylol or chloroform 
are commonly used — for four to five hours. The fluid should 
be changed several times. Then it is put in a mixture of chloro- 
form or xylol and paraffin for two to three hours. The infiltra- 
tion is hastened by heating the mixture at about 50 C. It is 
then placed in paraffin that melts at about 50 C. for three to 
five hours, the paraffin having been changed once or twice. 
The melting-point can be varied by making combinations of 
paraffin that melt at different degrees. The two generally 
used are one of 56 C. and another of 45 ° C. In warmer weather 
a paraffin with a higher melting-point is used. 

The specimen is taken and placed in a little paper box in 
which a small amount of paraffin has been poured. When the 
tissue has been properly arranged, more paraffin is added. 
The box is then placed in a dish of cold water, so that it will be 
rapidly cooled. This prevents crystallization and brittleness. 
Instead of using the paper boxes two right angles of metal are 
put on a glass plate so as to form an enclosure. Paraffin is 
poured in to form a thin film, then the tissue, and finally more 
paraffin. 

After cooling, the specimen is fastened on a block of vulcanite 
or hard paraffin by heating its surface, and is then cut on the 
microtome. The blade is held at a right angle if the specimen 



PARAFFIN METHOD 285 

is small, on a slant if large, and the cutting is done dry, no 
alcohol being used. 

Summary of the paraffin embedding: 

1. Dehydration in absolute alcohol. 

2. Xylol or chloroform four to five hours, changing the 

fluid a couple of times. 

3. Xylol or chloroform and paraffin, two or three hours. 

4. Melted paraffin in hot chamber at 50 C. for three to 

five hours. Change once. 

5. Block and quickly cool. 

6. Cut. 

The paraffin sections are so brittle that they cannot be 
treated in the same way as the celloidin ones. The best method 
is to take the section and place it in a dish containing water at 
about 45 C. This causes the specimen to flatten. A perfectly 
clean slide is then smeared with a very fine film of glycerin- 
albumin and is slipped under the floating section. The excess 
of water is drained off or carefully touched with blotting-paper 
and the slide is then placed in the incubator at 3 7 C. for three 
to five hours. 

The paraffin should be removed before staining the section. 
This is hastened by holding the slide over a small flame until 
the paraffin becomes transparent, when it is placed in xylol or 
turpentine for about two minutes. From there into absolute 
alcohol for about five minutes. It is advisable but not necessary 
to put the slides into weaker alcohol before beginning the stain. 
When the above steps have been gone through the tissues may 
be stained any way that is desired. 

Glycerin-albumin solution for fastening paraffin sections 
to the slide is made as follows: The white of an egg is well 
beaten and to it is added an equal volume of glycerin. These 
are thoroughly mixed and filtered. It is used by smearing a 
very thin layer on the slide, the paraffin section is placed on it 
and then heated up to a temperature of about 6o° C. until the 
albumin coagulates. If the sections have been taken from 
water it must be allowed to evaporate before the coagulating is 
done. The evaporation will be hastened by placing the slides 
in the incubator. 



286 LABORATORY TECHNIC 



CUTTING SECTIONS 






Freezing Microtome. — This method is valuable for rapid 
diagnostic work, but sections cannot often be cut sufficiently 
thin to allow a careful examination of the details. 

The piece of tissue used should not be more than 4 mm. 
high and it must be free from all traces of alcohol. The alcohol 
is removed by placing the specimen in a large amount of water 
that is of a temperature of about 30 C. 

The specimen is placed on the metal stand and a spray of 
ether or of carbonic acid gas is directed against the under side. 
The tissue is held in place by lightly pressing upon it with some 
flat piece of wood, as the handle of a small scalpel. Care must 
be taken not to freeze the tissue too hard or it will be so brittle 
as to break or show irregular streaks. The cut sections should 
be placed in 80 per cent, alcohol, as they will unroll better than 
if put directly into water. 

The freezing method is particularly well adapted for tissues 
that have been hardened in Muller's fluid, as there is no change 
in the finer characteristics. Formalin is very useful, as it 
permits very good sections to be made and is employed especially 
in the rapid diagnosis of tumors. 

A rapid method is as follows : 

1. Take a small portion of the tissue that has been removed 
at the operation and place immediately in a 10 per cent, solu- 
tion of formalin for about two minutes. 

2. Freeze; put the sections into water to flatten. 

3. Stain in lithium carmin two to three minutes. 

4. Blot stain and mount in glycerin. 

Serial Sections. — Paraffin. — The block containing the speci- 
men is turned until the anterior and posterior edges are parallel ; 
as much of the paraffin being removed as is possible. The knife 
is placed at right angles and with rapid strokes the sections are 
cut. The edges of the sections cling to each other and long 
ribbons may be cut. These ribbons should be carefully placed 
on sheets of toilet paper, carefully numbered and marked, so 
that the beginning of each series can be determined. The 
ribbons are divided into lengths convenient for placing on the 



STAINING 287 

slide. They are then floated on water and picked up on the 
slide covered with the glycerin-albumin. 



STAINING 

The principle of staining depends upon the different affinity 
of certain portions of the tissue for special dyes, so that they 
become more evident for purposes of study. There are certain 
stains which show a distinct affinity for the nuclei, while others 
select the cell protoplasm and the intercellular substance. By 
employing two stains a double coloring is obtained. In some 
conditions a single color may affect different portions of the 
tissue differently. 

According to their reaction, stains are divided into the basic, 
which are commonly nuclear or chromatin stains, and the acid, 
those that affect the cell protoplasm or the intercellular tissue. 
Neutral stains are generally artificial combinations of some of 
the above two. 

After being stained it is generally well to differentiate. Al- 
though a stain may be a nuclear one, yet there is usually some 
effect upon the other substances, the same holding true in 
regard to the acid stains. To remove this color, certain fluids 
are used, as water, weak solutions of acid in water or alcohol, 
alcohol, anilin oil, and tannic acid. 

It is also necessary that the sections shall be rendered trans- 
parent, and this is brought about by placing them in xylol, 
carbol-xylol, oil of cloves, creosote, or bergamot. 

Certain general rules should be observed: 

1. All staining fluids should be filtered before use to avoid 
precipitates in the tissue. Good stains should be used; the best 
being those of Dr. Griibler, of Leipzig. 

2. The sections should be spread out in the stain and should 
not lie upon each other, as the fluid is then likely to stain 
unevenly. Large amounts of stain in large dishes should be 
employed. It is also an advantage to carefully move the 
sections to and fro. 

3. The time required for staining varies, as a rule being less 
in old, well-ripened stains than in others freshly prepared. This 



288 LABORATORY TECHNIC 

depends also upon the proper hardening and fixation of the 
tissue and also upon its age. Fresh tissues will stain more 
deeply and more quickly than old ones. 

4. The staining of refractory tissues may be assisted by: 

(a) Concentration of the stain. 

(b) Staining for a longer time, up to twenty-four hours. 

(c) Heating up to 37 C. 

(d) Adding mordants, as acids and alkalis, anilin oil, 
etc. 

5. The sections should be carefully washed in water to remove 
all traces of the decolorizing agents used. 

6. Sections should be thoroughly dehydrated before being 
mounted; otherwise those areas containing water will not be 
transparent and will contain what appear to be oval pigment 
particles. 

Method of staining and mounting sections. 

1. Stain. 

2. Wash, usually in distilled water. 

3. Alcohol (80 per cent.) two to three minutes. 

4. Alcohol (95 per cent.) three to five minutes. 

5. Absolute alcohol two to three minutes. 

6. Clearing fluid until the specimen sinks below the surface, 

two to three minutes. 

7. Place section on slide, blot off the excess of clearing fluid, 

and mount in balsam, using a cover-glass. 

NUCLEAR STAINS 

Aqueous Alum Hematoxylin Solution. — 

Hematoxylin crystals 1 gm. 

Sat. aq. sol. ammonia alum 100 c.c. 

Water 300 " 

Thymol a crystal 

Dissolve the hematoxylin in a little water by the aid of 
heat. After the solutions have been mixed, expose to the 
light and air in an unstoppered bottle for about ten days. 
Then tightly cork. 



HEMATOXYLIN STAINING 289 

Delafield's Hematoxylin. — 

Hematoxylin crystals , 4 gm. 

Alcohol (95 per cent.) 25 c.c. 

Sat. aq. sol. ammonia alum 400 " 

Dissolve the hematoxylin in the alcohol, then add the alum 
solution. Expose the mixture to the air and light four to five 
days. Then filter and add: 

Glycerin 100 c.c. 

Alcohol (95 per cent.) 100 " 

Expose to light and air for a couple of weeks, then filter and 
keep tightly corked. The solution lasts well and stains the 
more rapidly the older it gets. 
Ehrlich's Acid Hematoxylin. — 

Hematoxylin crystals 2 gm. 

Absolute alcohol 60 c.c. 

Glycerin 60 " ] saturated 

Water 60 " [ with am- 

Glacial acetic acid 3 " j monia alum. 

The solution is ripened in an uncorked bottle until it becomes 
deep red in color; requires a couple of weeks. If kept in well- 
stoppered bottle precipitates do not form and the solution 
retains its staining powers for years. Also does not overstain. 
Mayer's Hematein. — When hematein is used, ripening is 
unnecessary, but the results from such stains are not as satis- 
factory as when hematoxylin is used: 

Hematein 0.4 gm. 

(Dissolve in a few drops of glycerin.) 

Alum 5.0 " 

Glycerin 30.0 c c 

Water 70.0 " 

Hematoxylin Staining. — The nuclei are stained blue. The 
older the solutions, the quicker they act and the deeper they 
stain. If the sections are overstained, the excess of color can 
be removed by placing them in hydrochloric acid alcohol until 
the proper color is obtained. The acid causes the blue to change 
to a brown, but the color is regained when the sections are 
placed in water. The acid should be thoroughly washed out; 
19 



290 LABORATORY TECHNIC 

this can be hastened by using water to which an equal amount 
of a saturated watery solution of lithium carbonate has been 
added. 

1. Stain three to ten minutes, according to age of stain. 

2. Wash thoroughly. 

3. Differentiate with acid alcohol, about thirty seconds if 

sections are overstained. 

4. Wash thoroughly. 

5. A counterstain, eosin, is usually employed 

6. Dehydrate, clear, and mount in balsam. 
Alum Carmin. — 

Carmin 1 gm. 

Alum solution (5 per cent.) 100 c.c. 

Boil for one-half to one hour and when cool filter. It stains the 
nuclei a violet red. There is no danger of overstaining and the 
color is not very easily removed in water or weak acid solutions. 
This preparation does not work well with objects that are diffi- 
cult to stain. 
The sections are placed: 

1. In the stain for ten minutes to two hours. 

2. Then washed thoroughly in distilled water. 

3. Dehydrated in alcohol, cleared, and mounted. 
Lithium Carmin. — 

Carmin 2.5 to 5.0 gm. 

Sat. sol. lithium carbonate 100.0 c.c. 

Heat and filter. The nuclei are stained an intense red. Is well 
adapted for tissues that stain with difficulty. Any excess of 
color can be removed in acid alcohol. Is a good counterstain 
for tissues that have been injected with blue substances. 
Sections are placed: 

1. In the stain for two to three minutes. 

2. Washed in water. 

3. Differentiated for one-half to one minute in acid alco- 

hol; hydrochloric acid, 1; 70 per cent, alcohol, 100. 

4. Washed thoroughly so as to remove the acid. 

5. Dehydrated in alcohol, cleared, and mounted in balsam. 



BISMARCK BROWN STAIN 29 1 

Picrolithium Carmin. — 

Lithium carmin solution 1 part 

Sat. watery sol. picric acid 2 parts 

Sections are: 

1. Stained three to five minutes. 

2. Washed. 

3. Differentiated two to three minutes acid alcohol. 

4. Washed thoroughly. 

5. Dehydrated in alcohol that has had a little picric acid 

added to it. 
7. Cleared and mounted. 
Nuclei are stained brownish red, and the protoplasm yellow. 
Borax Carmin. — 

Carmin : 0.5 gm. 

Borax 2.0 " 

Distilled water 100.0 c.c. 

Mix and heat until boiling begins; should be stirred constantly; 
then add 4.5 parts of dilute acetic acid (0.5 per cent.) and let 
stand twenty-four hours; then filter. 

This gives the same results as the lithium carmin except that 
the color is not so intense. 

Sections placed: 

1 . In stain for five to fifteen minutes. 

2. Washed in water. 

3. Differentiated one-half to one minute in acid alcohol 

solution. 

4. Washed in water thoroughly to remove acid. 

5. Dehydrated, cleared, and mounted. 
Bismarck Brown. — 

Either a 3 to 4 per cent, watery solution obtained by 

boiling and filtering. 
Or a concentrated alcoholic solution made in 40 per cent, 
alcohol, equal to 1 J to 2 per cent. 
Sections are: 

1. Stained five minutes. 

2. Washed in alcohol or 1 per cent, hydrochloric acid alcohol. 

3. Dehydrated, cleared, and mounted. 



292 LABORATORY TECHNIC 

The nuclei are stained a deep brown; the protoplasm, a 
lighter color. Bacteria are an intense brown. Cannot over- 
stain. This method is especially adapted for micro-photographic 
work. 

Gentian- violet. — Either a i per cent, watery or a 2 per cent, 
alcoholic solution may be used. Are likely to overstain. 

Sections are: 

1. Stained three to five minutes. 

2. Washed in alcohol until they become a pale blue. 

3. Then in absolute alcohol. 

4. Cleared and mounted. 

The nuclear staining is clearer if the sections are put for 
fifteen to thirty seconds in a 0.5 per cent, solution of acetic 
acid and then into the alcohol. 

Safranin is usually employed after fixing in Flemming's 
solution to bring out karyokinetic figures. 

Sections : 

1. Stained one-half to twenty-four hours in a 1 per cent. 

watery solution of safranin. 

2. Quickly washed in water. 

3. Washed in absolute alcohol to which 5 to 10 drops of 1 

per cent, hydrochloric acid alcohol have been added. 

4. Washed in pure absolute alcohol until the section is a 

clear brown. 

5. Cleared and mounted in alcohol. 

The resting nuclei are pink, those undergoing mitotic changes 
are deep red. 
Another method is: 

Anilin oil. . 2 ex. 

Water 100 " 

Safranin in excess. 

Heat to 6o° C. and filter. The solution will last about two 
months. This form stains almost immediately. The after- 
steps are as above. 



EOSIN 293 

DIFFUSE AND DOUBLE STAINING 

Double staining is employed for the purpose of obtaining 
a contrast between the nuclei and the plasms and interstitial 
substance. The nuclear stain is employed first, as the contrast 
stain is weaker and colors the tissues more diffusely. 

Neutral Carmin. — 

Carmin powder 5 gm. 

Aq. ammon. fort 1 c.c. 

These rubbed together, then add: 

Distilled water 200 c.c. 

Boil until the ammonia is driven off. Allow the solution to 
stand uncorked for about a week, then filter. The solution 
works better as it becomes older. 

To prepare the stain for immediate use add just enough 
ammonia to the carmin to make a paste. This should be 
thinly spread on the sides of the mortar and allowed to dry. 
Pulverize again, let it remain exposed to the air for twenty- 
four hours, then dissolve in cold water ; it is then ready for use. 

To stain sections: Add the stock solution to distilled water 
until a clear pale red color results. The sections remain in this 
until they become plainly red, up to twelve hours. The best 
results are obtained by staining for a long time in a weak solu- 
tion. Strong solutions stain more rapidly. Wash thoroughly 
in water, dehydrate, clear, and mount. 

The counterstain best used is hematoxylin, and it should 
be employed first. 

Eosin. — Either the form soluble in water, which is the better, 
or that in alcohol may be used. A few drops of a concentrated 
solution of either variety is added to a small dish of water and 
the sections stained until they are of a reddish color — one to 
three minutes. 

Then washed in water. 

Dehydrated in alcohol. Should be careful not to leave in the 
alcohol too long, as it gradually dissolves out the stain. 

Cleared and mounted. 

This method is preceded by staining in hematoxylin. In 
such cases the nuclei are blue. In specimens fixed in formalin 



294 LABORATORY TECHNIC 

or sublime solutions the red blood-cells stain a bright red or 
copper color and the blood-vessels are prominent. Eosinophile 
cells show up plainly. The other tissues show a diffuse reddish 
tinge. 

Picric acid is generally used in combination with some other 
stain, as in Van Gieson's method. As the picric acid decolorizes 
the sections, they should be overstained in the hematoxylin. 
If iron hematoxylin is used instead of Delafield's, the decoloriza- 
tion does not occur to the same extent. 

Van Gieson's method for nervous tissue: 

Aqueous sol. acid fuchsin (i per cent.) 15 c.c. 

Sat. aq. sol. picric acid .- 50 " 

Water 50 " 

For connective tissue: 

Aq. sol. acid fuchsin (1 per cent.) 5 c c. 

Sat. aq. sol. picric acid .- 100 " 

Sections are: 

1. Overstained in Delafield's hematoxylin. 

2. Washed thoroughly in water. 

3. Stained in Van Gieson solution three to five minutes. 

4. Washed in water one-half minute. 

5. Dehydrated, cleared, and mounted. 

Nuclei are stained brownish red; connective tissue, varying 
shades of light red; axis-cylinders, brownish red; myelin sheaths, 
yellow; neuroglia and sclerosed fibers, red; amyloid, rose or 
reddish brown; hyaline, red; colloid, orange or red. 

CONNECTIVE TISSUE STAINS 
Van Gieson's stain, as already given, may be used. The 
best results are obtained after fixation in chrome salts or sub- 
limate solutions; are not so good after alcohol. 

Mallory's anilin blue stain gives good results after fixation 
in Zenker's fluid or sublimate solutions. The fibrillar and reticu- 
lum of connective tissue, amyloid, mucous, and other hyaline 
substances stain blue; the connective tissue can be differentiated 
from the other substances by their form. Nuclei, protoplasm, 
fibroglia, fibrils, axis-cylinders, neuroglia fibers, and fibrin stain 



UXXA S ORCEIN STAIX 295 

red: erythrocytes and myelin sheaths, yellow: elastic fibers, pale 
pink or yellow. 
Sections are: 

1. Stained in a 0.1 per cent, aqueous solution of acid fuchsin 

five or more minutes. 

2. Transfer to the following solution and stain twenty 

minutes or more: 

Anilin blue soluble in water (Grubler) 0.5 gm. 

Orange G. (.Grubler) 2.0 u 

Aqueous solution of phosphomolybdic acid (1 per 

cent.) 100.0 c.c. 

3. Wash and dehydrate in several changes of 95 per cent. 

alcohol. 

4. Clear in xylol or in oil of origanum (Cretici). 

5. Balsam. 

ELASTIC FIBER STAIN 

Weigert's Stain for Elastic Fibers. — It is best to buy the 
stain already made up. as its preparation is rather difficult. 
The sections are: 

1. Stained in the above solution for twenty minutes to one 

hour. 

2. Washed off in alcohol. 

3. Blotted with filter-paper, xylol added, and blotted 

two or three times until the section is clear. 

4. Mounted in balsam. 

The elastic fibers are dark blue, almost black. 
Unna's Orcein Stain. — 

Orcein 1 gm. 

Hydrochloric acid 1 c.c. 

Absolute alcohol 100 " 

Sections are: 

1. Stained six to twenty-four hours. 

2. Washed thoroughly in 70 per cent, alcohol. 

3. Washed in water to get rid of the acid. 

4. Dehydrated, cleared, and mounted. 

The elastic fibers are a deep silky brown color: connective 
tissue, a pale brown. This method has the advantage that 



296 LABORATORY TECHNIC 

elastic fibers that have degenerated into elacin take the basic 
blue stain. 

Levaditi Stain for Treponema Pallidum. — 

1. Fix small pieces of tissue, 1 to 2 mm. thick, in 10 per 

cent, formol for twenty-four hours. 

2. Wash in water a few minutes; place in 95 per cent. 

alcohol for twenty-four hours. 

3. Wash in distilled water until the tissue sinks. 

4. Place in a 2 per cent, solution of silver nitrate and 

put in an incubator at 38 ° C. for three to five days. It 
is best to use amber-colored bottles. 

5. Wash briefly in distilled water, then put in the following 

solution for twenty-four to forty-eight hours at room- 
temperature : 

Pyrogallic acid 3 gm. 

Formalin 5 ex. 

Aq. dest 100 " 

6. Wash in water, dehydrate, and embed in paraffin. The 

treponema will stain black; the rest of the tissue, yellow. 
Kaiserling's Method of Preserving Natural Colors in Tissues. 

1. Fixation for one to five days in — 

Formaldehyd 200 c.c. 

Water 1000 " 

Nitrate of potassium 15 gm. 

Acetate of potassium 30 " 

Change the position of the specimen frequently. The time 
of fixation varies with the tissue or organ and the size of the 
specimen. 

2. Drain and place in 80 per cent, alcohol one to six hours, 

and then in 95 per cent, alcohol for one to two hours, to 
restore the color. 

3. Preserve in — 

Acetate of potassium 200 gm. 

Glycerin , 400 c.c. 

Water 2000 " 

Exposure to light gradually affects the colors. 



BLOOD STAINING 297 

BLOOD STAINING 

Before being stained the blood must be fixed to the slide 
either by heat or by some chemical. 

Heat may be used in all cases except when Wright's stain 
is employed; it must be used with Ehrlich's triple stain to get 
good results. The films should be exposed to a dry heat of from 
ioo° to no° C. for ten to fifteen minutes. 

Chemicals. — The smears are fixed in absolute alcohol or ether 
or a mixture of equal parts of the two for five to ten minutes. 
Then dried and stained. 

Stains. — Wright's. — It is best to procure this stain ready 
made. It is employed as follows, as no previous fixing is neces- 
sary: 

The unfixed film is covered with the solution and stained for 
a minute. Distilled water is added drop by drop until a metallic 
scum appears on the surface of the fluid and is allowed to remain 
two to three minutes. Then wash the film, which is a deep blue 
or purplish color, until it becomes yellowish or pink. Dry 
between blotting-paper and mount in balsam. 

The erythrocytes will be stained orange or pink; the nuclei 
of the leukocytes, blue; neutrophile granules, lilac; eosinophile 
granules, pink; fine basophile granules, deep blue; coarse mast- 
cell granules, deep purple. The malarial organism stains blue. 

Ehrlich's Triacid. — Best bought ready made. 

After fixing with heat, stain five to eight minutes; wash in 
running water, dry, and mount. 

Erythrocytes stain orange ; nuclei of the leukocytes, greenish 
blue; neutrophile granules, violet or lavender; eosinophile 
granules, copper red; basophile granules are unstained. 

Polychrome methylene-blue (Goldhorn's) is bought ready 
made. 

After fixation for fifteen to twenty seconds in methyl-alcohol, 
wash in water and, without drying, stain for one to two min- 
utes. Wash thoroughly in running water, dry with blotting- 
paper, and mount. 

This method shows very well granular degenerations of the 
erythrocytes, the nuclei of erythroblasts and leukocytes, baso- 



290 LABORATORY TECHNIC 

philic granules, and most bacteria. It is a very good stain for 
the malarial organism. If the film is first stained for ten to 
fifteen seconds in a 0.1 per cent, aqueous solution of eosin, 
washed, and then the methylene-blue used, a very good picture 
of the acid-coloring elements is given. 

Eosin and Methylene-blue. — Fix the smear in absolute alcohol 
alone or mixed with an equal quantity of ether. Stain in a 0.5 
per cent, solution of eosin in absolute alcohol, to which an equal 
quantity of water is added, for about five minutes without heat- 
ing. Wash and dry, then counterstain in a saturated aqueous 
solution of methylene-blue for about one minute. Wash again, 
dry, and mount. 

Gives a good picture of the nuclei of the basophilic granules 
and of the malarial organism: eosinophile granules stain red; 
the protoplasm of the polymorphonuclear leukocytes colors a 
slight pink; the granules remaining unstained. 



INDEX 



Abbott's method of spore staining, 

209 
Abscess, 87 

definition of, 87 

embolic, 87 

metastatic, 87 

pyemic, 87 
Acetone in diabetes, 29 
Achlorhydria, 23 
Acromegaly, 26, 112 
Actinomyces, 183, 184 

bovis, 181, 245 

farcinica, 245 

madurae, 106, 245 
Actinomycosis, 104, 172 

of bones, 105 

of lungs, 105 
Adami's classification of tumors, 122 

theory of tumor formation, 117 
Addison's disease, 26, 65 
Adenocarcinoma, 159 
Adenocystoma, 152 
Adenoma, 150 
Adenomatous polyp, 151 
Adipocere, 56 
Adrenals, abnormalities of secretion, 

26 
Aerobes, 188 
Aerogenesis, 191 
Aerogens, 190 
Agar- agar, 200 
Agglutinins, 266 

Aggressive forces of infection, 254 
Alcohol, 277 
Algor mortis, 73 
Alimentary glycosuria, diabetes and, 

27 
Alum carmin, 290 
Alveolar sarcoma, 130 
Amphitricha, 187 



Amyloid bodies, 62 

degeneration in anesthetic leprosy, 
102 

metamorphosis, 60 
Amylopsin, 23 
Anabolic metabolism, 22 
Anabolism, 22 
Anaerobes, 188 
Anaerobic cultures, 203 
Anaphase, 79 
Anaphylaxis, 267 
Anaplasia, 114 
Anasarca, 51 
Anemia, 168 

local, 39 
Anesthetic leprosy, 102 
Angina, Ludwig's, 180 

Vincent's, 179 
Angioma, cavernous, 141 

plexiform, 141 

simplex, 140 
Angiosarcoma, 131 
Anilin gentian-violet stain, 207 
Animal parasites and disease, 21 
Anthracosis, 66 

of lung, 66 
Antibiosis, 189 
Antiseptics, 189, 192 
Antitoxin, diphtheria,preparation,27 1 

manufacture, 270 

tetanus, 273 
Aphthous stomatitis, 169 
Aplasia, definition of, 52 
Apnea, 24 

Apoplexy, cerebral, 41 
Aqueous alum hematoxylin solution, 

288^ 
Argyria, 66 
Arnold's method of maceration, 275 

steam sterilizer, 194 

299 



3°° 



INDEX 



Arteries, vasomotor changes in, 36 
Arterioliths, 46 
Ascites, 51 
Asphyxia, 24 
Atrophy, 52 

brown, 39, 53, 66 
Attraction sphere, 76 
Autoclave, 195 
Auto-intoxication, 20 



Bacillus, 183 

anthracis, 229 

capsulatus mucosus, 220 

coli communis, 237 

diphtheriae, 225 

dysenteriae, 240 

Friedlander's, 219 

fusiformis, 251 

influenzae, 232 

lactis aerogenes, 220 

leprae, 99, 244 

mallei, 102 

cedemati maligni, 230 

of Bordet-Gengou, 239 

of Koch-Weeks, 239 

paratyphoid, 237 

pestis, 238 

pneumoniae, 219 

pyocyaneus, 215 

tetani, 222 

tuberculosis, 240 

typhosus, 233 
Bacony disease, 61 
Bacteria, 181 

and disease, 21 

classification of, 183 

examination of, 205 

growth of, 188 

higher, 182 

motility of, 185 

reproduction of, 187 

size of, 187 

staining of, 205 

structure of, 185 
Bacteriaceae, 183 
Bacterial proteins, 257 
Bacterin, preparation of, 273 
Bacterination, 273 
Bacterioproteins, 190 
Bacterium, 183 
Barometric pressure, effects of, 20 



Basedow's disease, 25 
Beggiatoaceae, 185 
Bichlorid of mercury, 196, 279 
Bile, 31 

pigments, Gmelin's test for, 65 

secretion, disorders of, 32 
Bilirubin, 65 
Biliverdin, 65 
Bismarck brown, 291 
Blastomyces dermatitis, 182 
Blastomycetes, 181 
Blood, staining of, for examination, 

297 
Blood-serum, 201 
Bones, actinomycosis of, 105 
Borax carmin, 291 
Bouillon, 199 

glucose, 200 
Bowhill's method of staining, 210 
Brown atrophy, 39, 53, 66 
Budding, 181 
Burns, duodenal ulcer from, 18 

effects of, 18 



Cachexia, 24 
Calcareous infiltration, 67 

of liver, 67 
Calcification, 67 
Calculi, 180 

Calmette's reaction, 243 
Capsules, staining of, 210 
Carbohydrates, 23 
Carbolfuchsin stain, 207 
Carbol gentian-violet stain, 207 
Carbolic acid, 196 
Carbol-thionin stain, 207 
Carcinoma, 153 

basocellulare, 158 

medullary, 154 

scirrhous, 154 

x-ray, 158 
Caseous necrosis, 70 
Catabolic metabolism, 22 
Catabolism, end-products of, 22 
Catarrhal stomatitis, 168 
Cauliflower growth, 118 
Caustics, effects of, 20 
Cavernous angioma, 141 
Cell, 75 

changes, qualitative, 53 
quantitative, 53 



INDEX 



30I 



Cell degenerations, 53 

functions of, 77 

infiltrations of, 53 

metamorphoses, 53 
Celloidin method of embedding, 283 
Cementoma, 146 
Centrosome, 76 
Cerebral apoplexy, 41 
Chalicosis, 66 
Chancre, 107 

Cheeks, malformations of, 167 
Chemotaxis, positive, 85 
Chlamydobacteriaceae, 184 
Chloasma, 66 
Chloroma, 132 
Chondroma, 137 

hyaline, 138 
Chondrosarcoma, 134 
Chorio-epithelioma, 163 

malignum, 164 
Chromatin, 75 

Chromic acid for decalcification, 280 
Chromogenesis, 191 
Chromogens, 190 
Cicatrization, 72, 90 
Circulatory disorders, 35 
Cladothrix, 182, 184 
Clostridium, 187 
Clothing, disinfection of, 197 
Cloudy swelling, 53 
Coagulation necrosis, 68 
Cohnheim's theory of tumor forma- 
tion, 115 
Cold, effects of, 19 
Colles' law, no 
Colliquation necrosis, 70 
Colloid metamorphosis, 59 
Complement-fixation, 268 
Concretions, 180 

Condyloma latum in syphilis, 109 
Congenital syphilis, no 

Wassermann reaction in, no 
Congestion, hypostatic, 36 
Connective tissue stains, 294 
Constipation, 34 
Coprostasis, 34 
Corpora amylacea, 62 
Cover-glass preparations, staining of, 

205 
Crenothrix, 184 
Cretinism, 25 
Crossed embolism, 47 



Croupous inflammation, 95 
Cryptococcus dermatitis, 182 
Culture-media, 199 

sterilization of, 194 
Cultures, anaerobic, 203 

potato, 201 

varieties of, 203 
Cutting sections, 286 
Cyanosis, 24 
Cylindroma, 131 
Cyst, definition of, 166 

dental, 148 

dermoid, 166 

exudation, 166 

liquefaction, 166 

of mouth, 174 

parasitic, 136 

retention, 166 
Cystoma, 166 
Cytoplasm, 75 

Death, 72 

signs of, 73 
Decalcification, 280 
Decomposition, 74 

signs of, 74 
Degeneration, 53 

cell, 53 

muscular, 66 

parenchymatous, 53 

Recklinghausen's, 59 
Dejecta, disinfection of, 197 
Delafield's hematoxylin, 289 
Demarcation, line of, 72 
Dendritic growth, 118 
Dental cysts, 148 
Dermoid cysts, 164, 166 

of mouth, 174 
Dermoids, ovarian, 164 
Diabetes, 27 

acetone in, 29 

and alimentary glycosuria, 27 

diacetic acid in, 29 

pancreatic, 28 
Diabetic coma, 29 
Diacetic acid in diabetes, 29 
Diapedesis, 84 

hemorrhage by, 42 
Diarrhea, causes of, 34 
Diffuse staining, 293 
Diphtheria antitoxin, preparation of, 

271 



302 



INDEX 



Diphtheric inflammation, 95 
Diplococcus intracellularis meningit- 
idis, 220 

pneumoniae, 217 
Disease, bacteria and, 21 

Basedow's, 25 

effect of seasons on, 20 

influence of foreign bodies in, 21 

lardaceous, 61 

thyroid gland in, 25 

waxy, 61 
Disinfection, 192 

of clothing, 197 

of dejecta, 197 

of furniture, 198 

of hands, 197 
Double staining, 293 
Dropsy, 50 

Dunham's peptone solution, 202 
Duodenal ulcer from burns, 18 
Dyspnea, definition of, 24 



ECCHONDROMA, 137 

Ecchymoses, 40 
Eclampsia, 30 
Edema, 50 

ex vacuo, 50 

neuropathic, 50 
Edematous infiltration, 63 
Ehrlich's acid hematoxylin, 289 

lateral-chain theory, 263 

triacid stain for blood, 297 
Electricity, effects of, 19 
Emaciation, 23 
Embedding, methods of, 282 

celloidin, 283 . 
Embolic abscess, 87 
Embolism, 46 

crossed, 47 

paradoxic, 47 

retrograde, 46 
Embolus, 46 

Emigration of leukocytes, 84 
Emphysema, interstitial, 51 
Empyema, 89 
Encapsulation, 72, 89 
Enchondroma, 137 
Endogenous infection, 253 
Endomyces albicans, 181 
Endothelioma, 132 
Endotoxins, 256 



End-products of catabolism, 22 
Eosin, 293 

and methylene-blue stain for blood, 

m 298 
Epistaxis, 41 
Epithelial pearls, 158 
Epithelioma, squamous, 157 
Epulis, 130, 135, 174 
Erlicki's fluid, 278 
Esmarch tube, 204 
Etiology, definition of, 17 
Eubacteria, 183 
Exfoliation, 72 
Exogenous infection, 253 
Exophthalmic goiter, 25 
Exophthalmos, 26 
Exoplasm, 75 
External secretions, 25 
Extraneous pigmentation, 66 
Extravasations, 40 
Exudates, 86 
Exudation cysts, 166 



Farcy, 103 

buds, 103 
Fat, metabolism of, 23 

necrosis, 72 
Fatty infiltration, 54 

metamorphosis, 56 
Fermentation, 190 
Fibrinous exudate, 86 
Fibroadenoma, 151 
Fibroblasts, 90 
Fibroma, 134 
Fibrosarcoma, 129 
Finkler-Prior spirillum, 251 
Fistula, 89 

of salivary ducts, 180 
Fixation, 277 

glycerin-albumin solution for, 285 
Flagella, staining of, 210 
Flemming's solution for fixation, 280 
Focal necrosis, 70 

Foreign bodies, influence in disease, 21 
Formaldehyd, 196 
Formalin, 277 
Freezing microtome, 286 
Friedlander's bacillus, 219 
Fungus, 118 

ray, 245 
Furniture, disinfection of, 198 



INDEX 



303 



Gangrene, 70 

dry, 71 

moist, 70 
Gangrenous stomatitis, 170 
Gelatin, 200 

glucose, 201 
Gentian- violet, 292 
Germicides, 189, 192 
Giant-cell sarcoma, 130 
Giant cells, 77, 90 
Gingivitis, 172 
Glanders, 102 

lymph-nodes in, 103 

metastatic abscesses in, 103 

of lungs, 103 
Glioma, 153 
Glossitis, 173 
Glucose bouillon, 200 

gelatin, 201 
Glycerin-albumin, solution for fixa- 
tion, 285 
Glycogenic infiltration, 62 
Glycosuria, alimentary, and diabetes, 

27 
Gmelin's test for bile-pigments, 65 
Goblet-cell, 59 
Goiter, exophthalmic, 25 
Gonococcus, 217 
Gout, 30 

Gram's method, 208 
Granulation tissue, 91 
Granulomata, 96 
Gumma, 109 

of mouth, 172 
Gymnobacteria, 187 



Hands, disinfection of, 197 
Hanging-drop cultures, 203 
Haptobacteria, 183 
Hardening, 277 
Hemangio-endothelioma, 133 
Hemangioma, 140 
Hematogenous jaundice, 65 
Hematoidin, 63 
Hematoma, 40 
Hematoxylin staining, 289 
Hematuria, 41 
Hemoglobin, 63 
Hemolysis, 21 
Hemopericardium, 41 
Hemophilia, 41 



Hemoplastic tumors, 119 

Hemoptysis, 4 

Hemorrhage by diapedesis, 39, 42 

by rhexis, 39, 41 

primary, 40 

results of, 42 

secondary, 40 

spontaneous arrest of, 42 
Hemorrhagic exudate, 86 
Hemosiderin, 63 
Hemothorax, 41 
Hepatogenous pigmentation, 65 
Hermann's fluid, 280 
Heterologous tumors, 119 
Heteroplasia, 114 
Heteroplastic tumors, 119 
Higher bacteria, 182 
Histoid tumors, 119 
Homologous tumors, 119 
Hormones, 25 
Hutchinson's teeth, in 
Hyaline chondroma, 138 

metamorphosis, 57 
Hyaloplasm, 75 
Hydatid mole, 163 
Hydrocele, 51 
Hydrocephalus, 51 
Hydrochloric acid for decalcification, 

281 
Hydrogen peroxid, 196 
Hydropericardium, 51 
Hydrops, 50 
Hydro thorax, 51 
Hyperchlorhydria, 23 
Hyperchromatosis, 153 
Hyperemia, 168 

active, 37 

general, 37 

local, 37 

passive, 37, 168 
Hyperglycemia, 27 
Hyperkeratosis, 158 
Hypernephroma, 152 
Hyperplasia, 112, 113 

compensatory, 113 

morbid anatomy of, 113 
Hypertrophy, 112 

compensatory, 112 

etiology of, 112 

false, 112, 113 

morbid anatomy of, 113 

true, 112 



3°4 



INDEX 



Hyphomycetes, 182 
Hypochlorhydria, 23 
Hypoplasia, definition of, 51 
Hypostatic congestion, 36 
pneumonia, 36 



Icterus, 32, 65 
Ileum in typhoid, 86 
Immunity, 259 

acquired, theories of, 260 
Incubation, period of, 252 
Infarction, 48 
Infarcts, anemic, 48 

hemorrhagic, 41, 48 

red, 48 

white, 48 
Infection, 252 

aggressive forces of, 254 

avenue of, 258 

cardinal conditions of, 17 

endogenous, 253 

exogenous, 253 

virulence of, 257 
Infectious disease, definition of, 21 
Infective theory of tumor formation, 

116 
Infiltration, calcareous, 67 

edematous, 63 

fatty, 54 

glycogenic, 62 

of cell, 53 

pigmentary, 63 

round-cell, 85 

serous, 63 

uratic, 68 
Inflammation, 82 

acute, 94 

adhesive, 95 

cardinal symptoms of, 85 

catarrhal, 94 

chronic, 94 

croupous, 95 

degenerative, 95 

desquamative, 95 

diphtheric, 95 

exudative, 94 

fibrinous, 94 

gangrenous, 95 

hemorrhagic, 94 

infectious, 94 

interstitial, 94 



Inflammation, non-infectious, 94 

of pharynx, 177 

of salivary glands, 179 

parenchymatous, 94 

phlegmonous, 95 

productive, 95 

products of, 86 

purulent, 94 

pustular, 95 

serous, 94 

specific, 95 

termination of, 89 

ulcerative, 95 

vesicular, 95 
Inflammatory exudates, 86 
Injection of specimens, 282 
Internal secretions, 25 
Interstitial emphysema, 51 
Intestine, disturbances in, S3 
Intoxication, 20 

endogenous, 20 
Irritants, 20 
Ischemia, 39 



Jaundice, 32, 65 
hematogenous, 65 
obstructive, 65 

Kaiserling's method of preserving 

natural colors in tissues, 296 
Karyokinesis, 78 
Karyolysis, 69 
Karyomitome, 75 
Karyoplasm, 75 
Karyorrhexis, 69 
Keloid, 135 
Koch's laws, 21 



Laboratory technic, 275 
Lardaceous disease, 61 
Leiomyoma of uterus, 140 
Lentigo, 66 
Leprosy, 99 
anesthetic, 102 

amyloid degeneration in, 102 
nerve, 101 
nodular, 100, 101 

lymph-glands in, 102 
susceptibility of lower animals to, 
99 



INDEX 



3°5 



Leptothrix, 182 

buccalis, 176 
Leptotricha, 187 
Leukocytes, emigration of, 84 
Leukoplakia of mouth, 172 
Levaditi stain for Treponema palli- 
dum, 296 
Line of demarcation, 72 

of ulceration, 72 
Lipoma, 135 

of shoulder, 137 
Lips, malformation of, 167 
Liquefaction cysts, 166 

necrosis, 70 
Lithium carmin, 290 
Litmus milk, 201 

Liver, calcareous infiltration of, 67 
Lividity, postmortem, 73 
Livores mortis, 73 

Loffler's method of staining flagella, 
210 

methylene-blue stain, 206 

mixture, 201 
Lower animals, leprosy in, 99 
Lud wig's angina, 180 
Lugol's solution, 276 
Lumpy jaw, 104 
Lungs, actinomycosis of, 105 

anthracosis of, 66 

in glanders, 103 

osteoma of, 139 

passive hyperemia of, 38 
Lymphangioendothelioma, 133 
Lymphangioma, 141 
Lymph-nodes in glanders, 103 
Lymphosarcoma, 128 
Lysins, 265 



Maceration, 275 

Arnold's method of, 275 
Macrocheilia, 174 
Macroglossia, 174 
Macrophages, 261 
Madura foot, 106 
Malaria, 65 
Malformations of cheeks, 167 

of lips, 167 
Mallory's anilin blue stain, 294 
Marasmus, 24 
Mast cells, 90 
Mayer's hematein, 289 



Medullary carcinoma, 154 
Melanin, 63, 65, 131 
Melanoglossia, 173 
Melanosis, 65 
Melanotic sarcoma, 65 
Meningococcus, 220 
Mercury bichlorid, 279 
Metabolic pigmentation, 65 
Metabolism, anabolic, 22 

catabolic, 22 

disorders of, 22 

of fats, 23 
Metamorphosis, amyloid, 60 

colloid, 59 

fatty, 56 

hyaline, 57 

mucoid, 59 

myxomatous, 59 

of cell, 53 
Metaphase, 78 
Metaplasia, 114 

Metastasis in malignant tumors, 120 
Metastatic abscess, 87 
Methylene-blue, Loffler's, 206 
Micrococcus, 183 

catarrhalis, 221 

gonorrhoeae, 216 

tetragenus, 222 
Micro-organisms, specific, 211 
Microphages, 261 
Microsomes, 75 
Microspira, 184 
Microtome, freezing, 286 
Moist gangrene, 70 
Molds, 182 
Mole, hydatid, 163 

pigmented, 66 

placental, 163 
Moller's method of staining spores, 

209 
Molluscum fibrosum, 135 
Monotricha, 187 
Morbid anatomy, 17 

histology, 17 

physiology, 17 
Morro test, 243 
Mouth, cysts of, 174 
dermoid, 174 

gumma of, 172 

leukoplakia of, 172 

tuberculosis of, 172 

tumors of, 174 



3° 6 



INDEX 



Mucin, 59 

Mucoid metamorphosis, 59 

Mucopus, 87 

Mucous patches, 109 

Miiller's fluid, 278 

Mummification, 70 

Mumps, 179 

Muscular degenerations, 66 

Mycetoma, 106 

Mycobacteriaceae, 184 

Myobacterium, 184 

Myoma, 139 

Myosarcoma, 134 

Myxangiosarcoma tubulare, 131 

Myxedema, 25 

Myxoma, 135 

Myxomatous metamorphosis, 59 

Myxosarcoma, 131 

Nasal secretions, Bacillus leprae in, 

101 
Necrobiosis, 53 
Necrosis, 68 

caseous, 70 

causes of, 69 

coagulation, 68 

colliquation, 70 

fat, 72 

focal, 70 

liquefaction, 70 
Neisser's stain for diphtheria bacillus, 

206 
Neoplasms, 115 

Nephritis in anesthetic leprosy, 102 
Nervous theory of tumor formation, 

117 
Neuritis in anesthetic leprosy, 102 
Neuroma, 139 
Neuropathic edema, 50 
Neurosarcoma, 134 
Neutral carmin, 293 
Nitric acid for decalcification, 281 
Nodular leprosy, 100, 101 
Noma, 170 
Nuclear stains, 288 
Nuclein, 75 
Nucleolus, 76 
Nucleus of cell, 75 



Obesity, 24 
Odontoma, 141 



Oidium albicans, 170 
Ophthalmotuberculin test, 243 
Opsonins, 274 
Oral sepsis, 172 
Organization, 72, 90 
Organoid tumors, 119 
Osmic acid, 279 
Osteoma, 137 
of lung, 139 
Osteosarcoma, 134 
Ovarian dermoids, 164 
Oxaluria, 31 



Pancreatic diabetes, 28 

Papilloma, 149 

Paradoxic embolism, 47 

Paraffin method of embedding, 284 

Paramucin, 59 

Paranucleus, 76 

Parasites, animal, 21 

Parasitic cysts, 166 

Parathyroids, 26 

Paratyphoid bacillus, 237 

Parenchymatous degeneration, 53 

Parotitis, 179 

Pasteurization, 195 

Pathogenesis, 191 

Pathogens, 190 

Pathology, definition of, 17 

Period of incubation, 252 

Perithelioma, 133 

Peritricha, 187 

Peroxid of hydrogen, 196 

Petechiae, 40 

Petri dish, 203 

Phagocytosis, theory of, 261 

Pharyngitis, 177 

Pharynx, inflammation of, 177 

tumors of, 179 
Phleboliths, 46 

Phloroglucin for decalcification, 281 
Phosphaturia, 31 
Photogens, 190 
Phragmidiothrix, 184 
Physiology, morbid, 17 
Picric acid for decalcification, 280 

for staining, 294 
Picrolithium carmin stain, 291 
Pigmentary infiltration, 63 
Pigmentation, extraneous, 66 

hepatogenous, 65 



INDEX 



307 



Pigmentation, metabolic, 65 
Pigmented moles, 66 
Pigments, biliary, 63 

Gmelin's test for, 65 

classification of, 63 

hematogenous, 63 

hepatogenous, 63 

metabolic, 63 
Pituitary body, abnormalities of, 26 
Placental mole, 163 
Planococcus, 183 
Planosarcina, 183 
Plasma cells, 90 
Plexiform angioma, 141 
Pneumococcus, 217 
Pneumonia, hypostatic, 36 
Pneumonokoniosis, 66 
Podagra, 30 
Poison, definition of, 20 
Polychrome methylene-blue for 

blood, 297 
Polyp, 118 

adenomatous, 151 
Polysarcia, 24 
Postmortem Hvidity, 73 

rigidity, 73 
Potato cultures, 201 
Precipitins, 266 
Prof eta's law, no 
Prophase, 78 

Proteids, metabolism of, 23 
Proteins, bacterial, 257 
Psammoma, 68, 132 
Pseudomonas, 183 
Pseudomucin, 59 
Psoriasis linguae, 173 
Ptomains, 190, 257 
Ptyalin, 23 
Purulent exudate, 86 
Pus, 87 

Putrefaction, 190 
Pyemic abscess, 87 
Pyopericardium, 89 
Pyorrhea alveolaris, 173 
Pyosalpinx, 89 
Pyrenin, 76 



Rachitis, 24 
Ranula, 174 
Ray fungus, 245 
Reaction, von Pirquet, 243 



Reaction, Wassermann, no, 268-270 
Recklinghausen's degeneration, 59 
Resolution, 89 
Retention cysts, 166 
Retrograde embolism, 46 
Retrogressive processes, 52 
Rhexis, hemorrhage by, 41 
Ribbert's theory of tumor formation, 

117 
Rickets, 24 
Rigor mortis, 73 
Rodent ulcer, 158 
Round-cell infiltration, 85 

sarcoma, 128 



Saccharomyces tumefaciens, 182 

Saccharomycetes, 181 

Safranin, 292 

Sago spleen, 62 

Salivary ducts, fistulae of, 180 

glands, inflammation of, 179 
tumors of, 180 
Salivation, 169 
Sanious pus, 87 
Saprogens, 190 
Sarcina, 183, 185 
Sarcoma, 125 

alveolar, 130 

giant-cell, 130 

melanotic, 65, 131 

round-cell, 128 

spindle-cell, 129 
Schizomycetes, 183 
Scirrhous carcinoma, 154 
Scirrhus, 154 

Seasons, effect on disease, 20 
Secretions, abnormalities of, 25 

external, 25 

internal, 25 
Sections, cutting of, 286 
Sepsis, oral, 172 
Sequestrum, 72 
Seropus, 87 
Serous exudate, 86 

infiltration, 63 
Shoulder, lipoma of, 137 
Sialoliths, 180 
Siderosis, 66 
Signs of death, 73 

of decomposition, 74 
Sinus, 89 



3 o8 



INDEX 



Slant cultures, 203 

Slough, 72 

Specific micro-organisms, 211 

Specimens, injection of, 282 

Sphacelus, 72 

Sphere of attraction, 76 

Spindle-cell sarcoma, 129 

Spirillacea?, 184 

Spirillum, 184 

cholerae asiaticae, 249 

of Finkler-Prior, 251 
Spirochseta, 184, 185 

buccalis, 248 

carteri, 249 

dentium, 248 

duttoni, 249 

novyi, 249 

pallida, 107, 246 

pertenuis, 248 

plicatilis, 248 

recurrentis, 249 

refringens, 247 

vincenti, 248 
Spirosoma, 184 
Spleen, sago, 62 
Spongioplasm, 75 
Sporadic teratoma, 165 
Spores, staining of, 209 
Sporotrichium, 104 
Sporotrichosis, 104 
Sporulation, 187 
Squamous epithelioma, 157 
Stab cultures, 203 
Stain, anilin gentian-violet, 207 

carbol gentian-violet, 207 

carbol-thionin, 207 

connective tissue, 294 

Loffler's methylene-blue, 206 

Neisser's, for diphtheria bacillus, 
206 

nuclear, 288 

picrolithium carmin, 291 

Unna's, for elastic fibers, 295 

Van Gieson's, 294 

Weigert's, for elastic fibers, 295 

Wright's, for blood, 297 
Staining, 287 

diffuse, 293 

double, 293 

of bacteria, 205 

Gram's method, 208 

of blood for examination, 297 



Staining of capsules, 210 

of cover-glass preparations, 205 

of flagella, 210 

Loffler's method, 210 
Bowhill's method, 210 

of spores, 209 

Abbott's method, 209 
Moller's method, 209 

with hematoxylin, 289 
Staphylococcus epidermidis albus, 
213 

pyogenes albus, 211 
aureus, 211 
citreus, 211 
Starvation, 23 
Stasis, 39 

Steam sterilizer, Arnold's, 194 
Steapsin, 23 
Sterilization, 192 

intermittent, 194 

of culture-media, 194 

table of, 193 
Stomatitis, 168 

aphthous, 169 

catarrhal, 168 

gangrenous, 170 

syphilitic, 172 

ulcerative, 168 
Streptococcus, 183 

pyogenes, 213 
Strep to thrix, 183 
Suffusions, 40 
Sugillations, 40 
Suppuration, 89 

organisms of, 211 
Susceptibility, 259 

of host, 259 
Swelling, cloudy, 53 
Symbiosis, 189 
Syphilis, 107 

condyloma latum in, 109 

congenital, no 

of tonsils, 176 

primary lesions of, 107 

secondary lesions of, 109 

tertiary lesions of, 109 
Syphilitic stomatitis, 172 



Tattoo marks, 65 
Technic, laboratory, 275 
Telophase, 80 



INDEX 



309 



Temperature, effects of, 18 
Teratoid tumors, 119 
Teratoma, 164 

sporadic, 165 
Test, Morro, 243 

ophthalmo tuberculin, 243 

Wassermann, no, 268-270 
Test-tubes, filling of, 202 
Tetanus antitoxin, 273 
Tetany, 26 
Thiobacteria, 185 
Thiothrix, 184 
Thoma's method of decalcification, 

282 
Thrombi, classification of, 44, 45 

liquefaction of, 46 

metamorphoses of, 45 
Thrombogen, 43 
Thrombokinase, 43 
Thrombosis, 43 
Thrombus, 42 

red, 44 

white, 44 
Thrush, 169 

fungus, 169 
Thyroid gland and disease, 25 

secretion, abnormalities of, 25 
Thyroidin, 25 

Tissue changes, progressive, 112 
Tonsillitis, 175 

leptothricia, 176 
Tonsils, syphilis of, 176 

tuberculosis of, 176 
Tophi, 68 
Toxalbumins, 190 
Toxic edema, 51 
Toxins, 190, 255 
Traumatism, 18 
Treponema pallidulum, 248 

pallidum, 107, 245 
Levaditi stain for, 296 
Trichloracetic acid for decalcification, 

282 
Trichobacteria, 184, 187 
Tuberculosis, 96 

of mouth, 172 

of tonsils, 176 

secondary, in anesthetic leprosy, 
102 
Tumors, 115 

Adami's classification of, 122 

benign, 120 



Tumors, causes of death from, 120 

classification of, 121 

definition of, 115 

epithelial, 149 

growth of, 119 

malignant, 120 
metastasis in, 120 

morphology of, 118 

of mouth, 1 74 

of pharynx, 179 

of salivary gland, 180 

predisposing causes of, 118 

theories of origin, n 5-1 17 
Typhoid, ileum in, 86 

Ulcer, 89 

duodenal, from burns, 18 

rodent, 158 
Ulceration, line of, 72 
Ulcerative stomatitis, 168 
Union by first intention, 92 

by second intention, 92 
Unna's orcein stain for elastic fibers, 

295 
Uratic infiltration, 68 
Uremia, 29 
Uterus, leiomyoma of, 140 



Van Gieson's stain, 294 
Vasomotor change* in arteries, 36 
Vibrio, 185 

metchnikovi, 251 

tyrogenum, 251 
Vincent's angina, 179 
Virchow's theory of tumors, 115 
Virulence of infection, 257 
Von Pirquet reaction, 243 

Wassermann reaction, no, 268-270 
Waxy disease, 61 

Weigert's stain for elastic fibers, 295 
Wright's stain for blood, 297 



X-ray carcinoma, 158 
effects of, 19 

Zenker's fluid, 279 
Zooglea, 185 
Zymogens, 190 



SAUNDERS' BOOKS 



Nervous and Mental 
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Dercum's Mental Diseases 

Mental Diseases. A Clinical Manual. By Francis X. 
Dercum, M. D., Ph. D., Professor of Nervous and Mental Dis- 
eases at Jefferson Medical College, Philadelphia. Octavo of 
425 pages. Cloth, S3. 00 net. 

TWO PRINTINGS IN FIVE MONTHS 

Dr. Dercum's work is along entirely new lines. It is strictly clinical. It 
is a book on mental diseases really useful to the family physician — a book 
that tells you how to diagnose, how to treat — either .at home or in an institu- 
tion — all classes of mental diseases ; tells you in a clear, simple way. There 
is no other book just like it. You are introduced at once into a clinical con- 
sideration of the various primary forms of mental disease, first taking up the 
affections you meet in your daily practice — delirium, confusion, stupor. 
Melancholia, mania, the insanities of early life, paranoia, the neurasthenic- 
neuropathic disorders, and the dementias follow in their turn. Then the 
mental disturbances of the infections, intoxications, metabolic disorders, visceral 
diseases, and diseases of the nervous system are taken up. An important 
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Church and Peterson's 
Nervous and Mental Diseases 



Nervous and Mental Diseases. By Archibald Church, 
M.D., Professor of Nervous and Mental Diseases and Head of 
Neurologic Department, Northwestern University Medical School, 
Chicago; and Frederick Peterson, M. D., Professor of Psy- 
chiatry in Columbia University, New York. Octavo, 934 pages, 
with 341 illustrations. Cloth, $5.00 net; Half Morocco, 
$6.50 net. 

THE NEW (7th) EDITION 

For this new seventh edition the entire work has been most thoroughly 
revised. To show with what thoroughness the authors have revised their 
work, we point out that in the nervous section alone over one hundred and 
fifty interpolations have been made, and, in addition, well over three hundred 
minor corrections. The section on Mental Diseases has been wholly re- 
arranged to conform to the latest classification, some obsolete matter struck 
out, and much new matter added. 

American Journal of the Medical Sciences 

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is two books. . . . The descriptions of disease are clear, directions as to treatment definite, 
and disputed matters and theories are omitted. Altogether it is a most useful text-book." 



Brill's Psychanalysis 

Psychanalysis : Its Theories and Practical Application. 
By A. A. Brill, M. D., Clinical Assistant in Neurology at 
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Cloth, $3.00 net. 

JUST OUT- NEW (2d) EDITION 

Tli is one volume gives you the practical application of all Freud's 
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is the only system of psychotherapy that deals with the neuroses as entities 
instead of treating symptoms as do hypnotism, suggestion, and persuasion. 
The results of psychanalysis are most effective. 



CHILDREN AND NURSING. 



Kerr's Diagnostics 
of Diseases of Children 



Diagnostics of the Diseases of Children. By LeGrand 
Kerr, M. D., Professor of Diseases of Children, Brooklyn Post- 
graduate Medical School, Brooklyn. Octavo of 542 pages, fully 
illustrated. Cloth, $5.00 net ; Half Morocco, $6.50 net. 

FOR THE PRACTITIONER 

In Dr. Kerr's work the objective symptoms are particularly emphasized. 
Differential diagnosis is discussed from the very earliest symptoms. The 
physician will find the many original illustrations a source of much informa- 
tion and help. 

New York State Journal of Medicine 

"The illustrations are excellent, and numerous. It will meet the needs of the great 
mass of physicians who treat the diseases of infancy and childhood." 



Kerley's New Pediatrics 

Practice of Pediatrics. By Charles Gilmore Kerley, M. 
D., Professor of Diseases of Children, New York Polyclinic 
Medical School and Hospital. Octavo of 878 pages, illustrated. 
Cloth, $6.00 net ; Half Morocco, $7.50 net. 

A NEW WORK— REPRINTED IN ONE MONTH 

This is an entirely new work — not a revision of Dr. Kerley's earlier work. 
It is not a cut-and-dried treatise — but the practice of pediatrics, giving, of 
course, fullest attention to diagnosis and treatment. The chapters on the 
newborn and its diseases, the feeding and the growth of baby, the care of 
the mother's breasts, artificial feeding, milk modification and sterilization, diet 
for older children — form a monograph of 125 pages. Then are discussed in 
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chapter on vaccine therapy is right down to the minute, including every new 
method of proved value — with the exact technic. There is an excellent 
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of certain abnormalities in which gymnastics have proved efficacious. 
Another feature consists of the i6j illustrative cases — case teaching of the 
most practical sort. 



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Grulee's Infant Feeding' 

Infant Feeding. By Clifford G. Grulee, M. D., Assist- 
ant Professor of Pediatrics at Rush Medical College. Octavo of 
314 pages, illustrated, including 8 in colors. Cloth, $3.00 net. 

JUST READY— NEW (2d) EDITION 

After reviewing the scientific principles bearing on the subject, Dr. Grulee 
goes into the actual application of them. He tells you how to feed the infant. 
He tells you — and shows by clear illustrations — the technic of giving the child 
the breast. Then artificial feeding is thoughtfully presented, including a 
number of simple formulas. The colored illustrations showing the actual 
shapes and appearances of stools are extremely valuable. 

Pediatrics 

" This work is the last word on infant feeding. It is a work that should be in the 
hands of every physician who is called upon to give advice where the subject of feeding 
babies and children is concerned.'" 



Keefer's Military Hygiene just Ready 

Military Hygiene and Sanitation. By Lieut. -Col. Frank R. 
Keefer, Professor of Military Hygiene, United States Military Academy, 
West Point. i2mo of 305 pages, illustrated. Cloth, #1.50- net. 

This is a concise though complete text-book on this subject, containing chapters on 
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marches, camps and battlefields, disposal of wastes, tropical and arctic service, 
venereal diseases, alcohol and other narcotics, and a glossary. 

Berg'ey's Hygiene Fourth Edition 

The Principles of Hygiene. By D. H. Bergey, A. M., M. D., 
Assistant Professor of Bacteriology, University of Pennsylvania. Octavo 
of 529 pages, illustrated. Cloth, $3.00 net. 

" It will be found of value to the practitioner of medicine and the practical sanita- 
rian ; and students, of architecture, who need to consider problems of heating, lighting, 
ventilation, water supply, and sewage disposal, may consult it with profit." 

Bi<ffalo Medical Journal. 



CHILDREN 



Ruhrah's Diseases of Children 

A Manual of Diseases of Children. By John Ruhrah, 
M. D., Professor of Diseases of Children, College of Physicians 
and Surgeons, Baltimore. i2moof 534 pages, fully illustrated. 
Flexible leather, $2.50 net. 

THE NEW (3d) EDITION 

The third edition makes this work more than ever the ideal desk book 
for the general practitioner. Although there have been added over one 
hundred pages of new matter and some sixty new illustrations, the book 
remains of a handy size and is still flexible. Among some of the amplified 
articles are those on the examination of sick children, food intoxications, 
bronchopneumonia, examination of the heart, and the nervous system. The 
section on therapeutics has been very largely rewritten, and that on the infec- 
tious diseases entirely rewritten. There has been added a table of doses, 
instructions for summer, care of the mentally deficient, the blind, and the deaf. 

American Journal of the Medical Sciences 

" Treatment has been satisfactorily covered, being quite in accord with the best teach* 
ing, yet withal broadly general and free from stock prescriptions." 



Griffith's Care of the Baby 

TheCare of the Baby. By J. P. Crozer Griffith, M. D., 
Clinical Professor of Diseases of Children, University of Penn- 
sylvania. i2mo of 455 pages, illustrated. Cloth, $1.50 net. 

THE NEW (5th) EDITION 
New York Medical Journal 

e< We are confident if this little work could find its way into the hands of every trained 
curse and of every mother, infant mortality would be lessened by at least fifty per cent." 



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Kaplan's Serology of Nervous 
and Mental Diseases 

Serology of Nervous and Mental Diseases. By D. M. 

Kaplan, M. D. , Director of Clinical and Research Laboratories, 

Neurological Institute, New York City. Octavo of 314 pages, 

illustrated. Cloth, $3.50 net. 

JUST READY 

This is an entirely new work on this subject. Here you get the newest 
technic — the application of serology in practice. You get the indications, 
contra-indications, preparation of patients, technic, after-phenomena, after- 
care, and disposal of the fluids obtained by lumbar puncture. You get the 
physical, chemical and cytologic properties of normal and pathologic fluids 
discussed in detail, including the interpretation of findings and bacteriology. 
You get a full discussion of the serology of all nervous and mental diseases 
of non-luetic etiology — meningeal affections (infectious and non-infectious), 
brain diseases, cord diseases, nerve affections (including disorders of 
internal secretion), the psychoses, and the intoxications. The serology of 
every type of luetic nervous and mental disease is next presented to you, 
giving the Wassermann reaction in detail, the use of salvarsan and neo- 
salvarsan. 



Hunt's Diagnostic Symptoms 
of Nervous Diseases 

Diagnostic Symptoms of Nervous Diseases. By 

Edward L. Hunt, M. D., Instructor in Neurology and Assist- 
ant Chief of Clinic, College of Physicians and Surgeons, New 
York. j2mo of 229 pages, illustrated. Cloth, #1.50 net. 

JUST READY 

Dr. Hunt gives you here those salient points and leading symptoms that 
will enable you to diagnose nervous and mental diseases. The book has 
chapters on examination, deformities, paralysis, tremors, trophic disorders, 
gaits, ataxia, convulsions, sensation, reflexes, eye symptoms, speech disturb- 
ances, aphasia, and electric reactions. The chapters on gaits takes up each 
gait in detail, giving you its characteristics and the diseases in which it occurs. 
Under reflexes the methods of eliciting the reflexes are clearly given and the 
diseases suggested by their absence stated. 



iVUXSIiVG. 



Sanders 9 Nursing 

Modern Methods in Nursing. By Georgiana J. Sanders, 

formerly Superintendent of Nurses at the Massachusetts General 

Hospital. i2mo of 88 1 pages, with 227 illustrations. Cloth, 

$2.50 net. 

COMPLETE 

Miss Sanders' book gives only modern methods. Then it gives the details 
of nursing operation cases, both in the hospital and in the home. The 
thorough way in which ward work is taken up makes her book indispensable 
for teaching purposes. In giving directions for mustard baths, poultices, etc., 
the quantities are given exactly. This is an important point often overlooked. 



Stoney's Nursing' 

Practical Points in Nursing : for Nurses in Private Practice. 
By Emily M. A. Stoney, formerly Superintendent of the Training 
School for Nurses at the Carney Hospital, South Boston, Mass. 
495 P a g es > fully illustrated. Cloth, $1.75 net. 



THE NEW (4th) EDITION 

In this volume the author explains the entire range of private nursing as 
distinguished from hospital nursing, and the nurse is instructed how best to 
meet the various emergencies of medical and surgical cases when distant 
from medical or surgical aid or when thrown on her own resources. An 
especially valuable feature will be found in the direction how to improvise 
everything ordinarily needed in the sick-room. 



Stoney's Technic for Nurses 

Bacteriology and Surgical Technic for Nurses. By 

Emily M. A. Stoney, Carney Hospital, South Boston. Re- 
vised by Frederic R. Griffith, M. D., Surgeon, N. Y. i2mo, 
311 pages, illustrated. $1.50 net. New (3d) Edition 



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Hoxie and Lapt&d's Medicine for Nurses New (2d) Edition 

Medicine for Nurses and Housemothers. By George Howard 
Hoxie, M. D., Physician to the German Hospital, Kansas City; and 
Pearl L. Laptad, formerly Principal of Training-School, University of 
Kansas. i2mo of 351 pages, illustrated. Cloth, $1.50 net. 

This work is truly a practice of medicine for the nurse, enabling her to recognize 
any signs and changes that may occur between visits of the physician, and, if neces- 
sary, to combat them until the physician's arrival. This information the author pre- 
sents in a way most acceptable, particularly emphasizing the nurse's part. There fare 
also special chapters on the diseases of the eye, ear, nose, and throat, venereal dis- 
eases, nervous and mental diseases, surgical nursing, emergency measures. 

" This book has our unqualified approval." — Trained Nurse and Hospital Review, 

McCombs' Diseases of Children for Nurses IditSn 

Diseases or Children for Nurses. By Robert S. McCombs, 
M. D., Instructor of Nurses at the Children's Hospital of Philadel- 
phia. i2mo of 460 pages, illustrated. Cloth, $2.00 net. 

Dr. McCombs has given a short but clear description of each disease found in 
infancy and childhood, so that the nurse will be enabled to know what symptoms to 
expect and what complications to guard against. 

" We have needed a good work on children's diseases adapted for nurses' use, and 
this volume admirably nllsThe want." — National Hospital Record. 

Wilson's Obstetric Nursing Stami Edmon 

A Reference Hand-Book of Obstetric Nursing. By W. Rey- 
nolds Wilson, M. D., Visiting Physician to the Philadelphia Lying- 
in Charity. 32mo of 258 pages, illustrated. Flexible leather, $1.25 
net. 

" Every page emphasizes the nurse's relation to the case.'' — American Journal oj 
Obstetrics. 

Fruhwald and Westcott on Children 

Diseases of Children. By Prof. Dr. F. Fruhwald, of Vienna. 
Edited by Thompson S. Westcott, M.D., University of Pennsylvania, 
Octavo, 533 pages, 176 illustrations. Cloth, $4.50 net. 

Boyd's State Registration for Nurses 

State Registration for Nurses. By Louie Croft Boyd, R.N., 
Graduate Colorado Training-school for Nurses. Octavo of 42 pages. 
50 cents net. 



DICTWXAKY 



American Illustrated Dictionary 

New (7th) Edition— 5000 New Words 

The American Illustrated Medical Dictionary. A new and 

complete dictionary of the terms used in Medicine, Surgery. 
Dentistry, Pharmacy, Chemistry, Veterinary Science. Nursing. 
and kindred branches ; with over ioo new and elaborate tables 
and many handsome illustrations. By W. A. Newman Borland, 
M. D. Large octavo, 1107 pages, bound in full flexible leather, 
$4.50 net; with thumb index, $5.00 net. 

Dorland's Dictionary defines hundreds of the newest terms not defined in any 
other dictionary — bar none. It gives the capitalization and pronunciation of 
all words. It makes a feature of the derivation or etymology of the words. 
In " Dorland " every word has a separate paragraph, thus making it easy to 
rind a word quickly. The tables of arteries, muscles, nerve:, veins, etc., with 
accompanying pictures in colors, are of the greatest help in assembling anatomic 
facts. In "Dorland" every word is civen its definition — a definition that 
defines in the fewest possible words. 

Howard A. Kelly, M. D., Johns Hopkins University , Baltimore. 

" Dr. Dorland's dictionary is admirable. It is so well gotten up and of such conve- 
nient size. No errors have been found in my use of it." 



Goodnow's First-Year Nursing illustrated 

First=Year Nursing. By Minnie Goodnow, R. N., formerly 

Superintendent of the Women's Hospital, Denver. i2mo of 325 pages, 
illustrated. Cloth, $1. 50 net 

Miss Goodnow' s work deals entirely with the practical side of first-year 
nursing work. It is the application of text-book knowledge. It tells 
the nurse how to do those things she is called upon to do in her first year 
in the training-school — the actual ward work. 

Roberts' Bacteriology and Pathology for Nurses 

Bacteriology and Pathology for Nurses. By Jay G. Roberts, 
Ph. G., M. D., Oskaloosa, Iowa. i2mo of 206 pages, illustrated. 

Cloth ; Si. 25 net. 
This new work is practical in the strictest sense. Written specially for 
nurses, it confines itself to information that the nurse should know. All 
unessential matter is excluded. The style is concise and to the point, 
vet clear and plain. The text is illustrated throughout. 



io SAUNDERS' BOOK'S ON 



Asher's Chemistry and Toxicology for Nurses 

Chemistry and Toxicology for Nurses. By Philip Asher, 
Ph. G., M. D., Dean and Professor of Chemistry, New Orleans Col- 
lege of Pharmacy. i2mo of 190 pages. 

Dr. Asher's one aim in writing this book was to emphasize through- 
out the application of chemical and toxicologic knowledge in the 
practice of nursing. This he has succeeded in doing. The nurse, 
both in training-school and in graduate practice, will find it extremely 
helpful, because the subject is made so clear. 

Aiken s' Home Nurse's Hand- Book 

Home Nurse's Hand-Book. By Charlotte A. Aikens. i2mo 
of 276 pages, illustrated. Cloth, $1.50 net. 

The point about this work is this : It tells you and shows you just how 
to do those little but important things often omitted from other 
nursing books. " Home Treatments " and " Points to be Remembered " 
— terse, crisp reminders — stand out as particularly practical. Just the 
book for those who have the home-care of the sick. 

Lewis' Anatomy and Physiology New (3d) Edition 

Anatomy and Physiology for Nurses. By LeRoy Lewis, M.D., 
formerly Surgeon to and Lecturer on Anatomy and Physiology for Nurses 
at the Lewis Hospital, Bay City, Michigan. i2mo of 344 pages, with 
161 illustrations. Cloth, #1.75 net. 

A demand for such a work as this, treating the subjects from the nurse's point of 
view has long existed. Dr. Lewis has based the plan and scope of this work on the 
methods employed by him in teaching these branches, making the text unusually 
simple and clear. 

" It is not in any sense rudimentary, but comprehensive in its treatment of the sub- 
jects in hand. The application of the knowledge of anatomy in the care of the 
patient is emphasized." — The Nurses Journal of the Pacific Coast. 

Friedenwald and Ruhrah's Dietetics New (3d) Edition 

Dietetics for Nurses. By Julius Friedenwald, M. D., Pro- 
fessor of Diseases of the Stomach, and John Ruhrah, M. D., Pro- 
fessor of Diseases of Children, College of Physicians and Surgeons, 
Baltimore. 1 2mo volume of 431 pages. Cloth, $1.50 net. 

This work has been prepared to meet the needs of the nurse, both in the training 
school and after graduation. It aims to give the essentials of dietetics, considering 
briefly the physiology of digestion and the various classes of foods and the part thev 
play in nutrition. ' 

"It is exactly the book for which nurses and others have long and vainly sought. 
A simple manual of dietetics, which does not turn into a cook-book at the end of the 
first or second chapter." — American Journal of Nursing. 



NURSiNG. 



Aikens' Primary Studies for Nurses N ew 2d) Edition 

PRIMARY Studies for Nurse- : A Text-Book for First-year Pupil 
Nurses. By Charlotte A. A i kens, formerly Director of Sibley Mem- 
orial Hospital, Washington, D. C. l2mo of 437 pages, illustrated. 
Cloth, S1.75 net. 

This work brings together in concise form well-rounded courses of lessons in all 
subjects which, with practical nursing technic, constitute the primary studies in a 
nursing course. 

Trained Nurse and Hospital Review 

" It is safe to say that any pupil who has mastered even the major portion of this 
work would be one of the best prepared first-year pupils that ever stood for examina- 
tion." 

Aikens* Clinical Studies for Nurses New (2d x <£&&** 

Clinical Studie- for Nurses. By Charlotte A. Aikens 
merly Director of Sibley Memorial Hospital, Washington, D. C. 121110 
of 569 pages, illustrated. Cloth, $2.00 net. 

This new work is written along the same lines as Miss Aikens' earlier work on 
" Primary Studies." to which it is a companion volume. It takes up all subjects 
taught during the second and third years and takes them up in a concise, forceful 
way. 

Dietetic and Hygienic Gazette 

" There is a large amount of practical information in this book which the experienced 
nurse, as well as the undergraduate, will consult with profit. The illustrations are 
numerous and well selected." 

Aikens' Training-School Methods and Head Nurse 

Hospital Training-School Methods and the Head Nurse. By 
Charlotte A. Aikens, formerly Director of Sibley Memorial Hospital, 
Washington, D. C. i2mo of 267 pages. Cloth, $1.50 net. 

Trained Nurse and Hospital Review 

" There is not a chapter in the book that does not contain valuable suggestions." 

Aikens' Hospital Management 

Hospital Management. By Charlotte A. Aikens, formerly Di- 
rector of Sibley Memorial Hospital. Washington, D. C. i2mo of 488 
pages, illustrated. Cloth, $3.00 net. 

The Medical Record 

" Tells in concise form exactly what a hospital should do and how it should be 
run, from the scrubwoman up to its financing. A valuable addition to our literature 
on this subject." 



SAUiVDEJiS' BOOKS ON 



StoneyV 
Materia Medica for Nurses 



Practical Materia Medica for Nurses, with an Appendix 
containing Poisons and their Antidotes, with Poison-Emergencies ; 
Mineral Waters ; Weights and Measures, etc. By Emily M. A< 
Stoney, formerly at the Carney Hospital, South Boston, Mass. 
i2mo, 300 pages. $1.50 net. 

THE NEW (3d) EDITION 

In this work the consideration of the drugs includes their names, their 
sources and composition, their various preparations, physiologic actions, 
directions for handling and administering, and the symptoms and treatment 
of poisoning. 

Journal of the American Medical Association 

" So far as we can see, it contains everything that a nurse ought to know in regard to 
drugs. As a reference-book for nurses it will without question be very useful." 



Bolduan and Grund's Bacteriology for Nurses 

Applied Bacteriology for Nursks. By Charles F. Bolduan, 
M.D., Assistant to the General Medical Officer, and Marie Grund, 
M. D., Bacteriologist, Research Laboratory, Department of Health, New 
York City. l2mo of 155 pages, illustrated. Cloth, $1.25 net. 

We were fortunate in getting these practical physicians to write this work. It 
gives particular emphasis to the immediate application of bacteriology to nursing, only 
the really practical being included. A study of all the modes of infection transmission 
is presented. At the end of each chapter are suggestions for practical demonstration. 

Bohm and Painter's Massage 

Massage. By Max Bohm, M. D., of Berlin, Germany. Edited, with 
an Introduction, by Charles F. Painter, M. D., Professor of Ortho- 
pedic Surgery at Tufts College Medical School, Boston. Octavo of 91 
pages, with 70 practical illustrations. Cloth, $1.75 net. 

Manhattan Hospital Eye, Ear, Nose, Throat Nursing 

Nursing in Diseases of the Eye, Ear, Nose, and Throat. By 
the Committee on Nurses of the Manhattan Eye, Ear, and Throat Hos- 
pital. i2mo of 260 pages, illustrated. Cloth, $1.50 net. 



NURSING AND CHILDREN. 



Paul's Fever Nursing New (2d) Edition 

Nursing in the Acute Infectious Fevers. By George P. Pail, 
M. I)., formerly Assistant Visiting Physician to the Samaritan Hospital, 
Troy, N. Y. i2mo of 246 pages. Cloth, #l.co net. 

Dr. Paul has taken great pains in the presentation of the care and management of 
each fever. The book treats of fevers in genera 1 , then each fever is discussed indi- 
vidually, and the latter part of the book deals with practical procedures and valuable 
information. 

" The book is an excellent one and will be of value to those for whom it is intended. 
It is well arranged, the text is clear and full, and the illustrations are good." — The 
London Lancet. 

Paul's Materia Medica for Nurses New (2d) Edition 

Materia Medica eor Nurses. By George P. Paul, M.I).. 
formerly Assistant Visiting Physician to the Samaritan Hospital, Troy. 
i2mo of 240 pages. Cloth, $1.50 net. 

Dr. Paul arranges the physiologic actions of the drugs according to the action 
of the drug and not the organ acted upon. An important section is that on pretoxic 
signs, giving the warnings of the full action or the beginning toxic effects of the drug, 
which, if heeded, may prevent many cases of drug poisoning. The nurse should 
know these signs. 

"This volume will be of real help to nurses ; the material is well selected and well 
arranged, and the book is as readable as it is useful." — The Medical Record. 

Pyle's Personal Hygiene The New (5th) Edition 

A Manual of Personal Hygiene : Proper Living upon a Physio- 
logic P>asis. By Eminent Specialists. Edited by Walter L. Pyle, 
A.M., M.D., Assistant Surgeon to Wills Eye Hospital, Philadelphia. 
Octavo volume of 515 pages, fully illustrated. Cloth, $1.50 net. 

To this new edition there have been added, and fully illustrated, chapters on 
Domestic Hygiene and Home Gymnastics, besides an appendix containing methods 
of Hydrotherapy, Mechanotherapy, and First Aid Measures. There is also a Glos- 
sary of the medical terms used. 

" The work has been excellently done, there is no undue repetition, and the writers 
have succeeded unusually well in presenting facts of practical significance based on 
sound knowledge." — Boston Medical and Surgical Journal. 

Galbraith's Four Epochs of Woman's Life second Edition 

The Four Epochs of Woman's Life. By Anna M. Galbraith, 
M.D. With an Introductory Note by John H. Musser, M.D., Univer- 
sity of Pennsylvania. l2mo of 247 pages. Cloth, #1.50 net. 

"We do not as a rule care for medical books written for the instruction of the 
public ; but we must admit that the advice in Dr. Galbraith's work is in the main 
wise and wholesome." — Birmingham Medical Review, Ettgland. 

Register's Fever Nursing 

A Text-Book on Practical Fevek Nursing. By Edward C. 
Register, M. D., Professor of the Practice of Medicine in the North 
Carolina Medical College. i2mo_of 352 pages. Cloth, $2.50 net. 

" Nurses will find this book of great value in this practical branch of their work.' 
— Trained Nurse and Hospital Review. 



14 SAUiVDERS' BOOKS ON 



Macfarlane's Gynecology for Nurses New (M) EdWott 

A Reference Hand-Book of Gynecology for Nurses. By 
Catharine Macfarlane, M. D., Gynecologist to the Woman's Hos- 
pital of Philadelphia. i6mo of 156 pages, with 70 illustrations. 
Flexible leather, $1.25 net. 

" This is a nut-shell book, and the flexible leather covers are full of meat." — Dietetic 
and Hygienic Gazette. 

Galbraith's Personal Hygiene and Physical Training 
for Women 

Personal Hygiene and Physical Training for Women. By 
Anna M. Galbraith, M.D.,, Fellow New York Academy of Medicine. 
i2mo of 371 pages, with original illustrations. Cloth, $2.00 net. 

Dr. Galbraith's book is just what has long been needed — a simple manual of hy- 
giene and physical training along scientific lines. 

De Lee's Obstetrics for Nurses New (4th) Edition 

Obstetrics for Nurses. By Joseph B. De Lee, M. D., Pro- 
fessor of Obstetrics in the Northwestern University Medical School. 
i2mo volume of 507 pages, fully illustrated. Cloth, $2.50 net. 

" It is far and away the best that has come to my notice, and I shall take great 
pleasure in recommending it to my nurses and students as well." — J. Clifton 
Edgar, M. D., Cornell Medical School, N. Y. 

Davis' Obstetric Nursing New (4th) Edition 

Obstetric and Gynecologic Nursing. By Edward P. Davis, 
A. M., M. D., Professor of Obstetrics, Jefferson Medical College and 
Philadelphia Polyclinic. i2mo of 480 pages, illustrated. Buckram, 
$1.75 net. 

" Not only nurses, but even newly qualified medical men, would learn a great deal 
by a perusal of this book. It is written in a clear and pleasant style, and is a work 
we can recommend." — The Lancet, London. 

Beck's Hand-Book for Nurses New (3d) Edit i on 

A Reference Hand-Book for Nurses. By Amanda K. Beck, 
of Chicago, 111. 32mo of 230 pages. Flexible leather, $1.25 net. 

This little book contains information upon every question that comes to 
a nurse in her daily work, and embraces all the information that she re- 
quires to carry out any directions given by the physician. 

" Must be regarded as an extremely useful book, not only for nurses, but for phys- 
icians." — Boston Medical and Surgical Journal. 



LEGAL MEDICINE 15 



Fiske's Human Body 

Structure and Functions of the Body. By Annette Fiske, 
A. M., Graduate of the Waltham Training School for Nurses. i2mo of 
221 pages, illustrated. Cloth, $1.25 net. 

Draper's Legal Medicine 

A Text-Book of Legal Medicine. By Frank Winthrop 
Draper, A. M., M. D., late Professor of Legal Medicine in Harvard 
University. Octavo of 573 pages, illustrated. Cloth, $4.00 net. 

Golebiewski and Bailey's Accident Diseases 

Atlas and Epitome of Diseases Caused by Accidents. By Dr. 
Ed. Golebiewski, of Berlin. Edited, with additions, hy Pearce Bailey, 
M. D., Consulting Neurologist to St. Luke's Hospital, New York. With 
71 colored illustrations on 40 plates, 143 text-illustrations, and 549 pages 
of text. Cloth, $4. 00 net. In Saunders' Hand- Atlas Series. 

Chapman's Medical Jurisprudence Third Edition 

Medical Jurisprudence, Insanity, and Toxicology. By Henry 
C. Chapman, M. D., late Professor of Institutes of Medicine and Med- 
ical Jurisprudence in Jefferson Medical College, Philadelphia. l2mo of 
329 pages, fully illustrated. Cloth, #1.75 net. 

Hofmann and Peterson's Legal Medicine J? ^"i"?*™' 

** Hand -Atlases 

Atlas of Legal Medicine. By Dr. E. von Hofmann, of Vienna. 
Edited by Frederick Peterson, M. D., Professor of Psychiatry in the 
College of Physicians and Surgeons, New York. With 120 colored 
figures on 56 plates and 193 half-tone illustrations. Cloth, S3. 50 net. 

Jakob and Fisher's Nervous System hJS&SI 

Atlas and Epitome of the Nervous System and its Diseases. 
By Professor Dr. Chr. Jakob, of Erlangen. Edited, with additions, 
by Edward D. Fisher, M. D., University and Bellevue Hospital 
Medical College, New York. With 83 plates and copious text. Cloth, 
#3-50 net. 

Peterson & Haines' Legal Medicine and Toxicology 

A Text-Book of Legal Medicine and Toxicology. Edited by 
Frederick Peterson, M. D., Columbia University, New York ; and 
Walter S. Haines, M. D., Rush Medical College. 

New Edition Preparing 



1 6 SAUNDERS' BOOKS ON NURSING. 

American Pocket Dictionary New (8th) Ediaon 

American Pocket Medical Dictionary. Edited by W. A. 
Newman Dorland, M.D. Containing the pronunciation and definition 
of the principal words used in medicine and kindred sciences, with 64 
extensive tables. With 677 pages. Flexible leather, with gold edges, 
$1.00 net ; with patent thumb index, #1.25 net. 

Morrow's Immediate Care of Injured tStlon 

Immediate Care of the Injured. By Albert S. Morrow, M. D., 
Attending Surgeon to the New York City Hospital for the Aged and In- 
firm. Octavo of 360 pages, with 242 illustrations. Cloth, $2.50 net. 

Crothers' Morphinism and Narcomania 

Morphinism and Narcomania. By T. D. Crothers, M. D. i2mo 
of 351 pages. Cloth, $2.00 net. 

Grafstrom's Mechano-Therapy 2d Revised Edition 

A Text-book of Mechano-therapy (Massage and Medical Gym- 
nastics). By Axel V. Grafstrom, B. Sc, M.D., Attending Physician 
to the Gustavus Adolphus Orphanage, Jamestown, New York. i2ino, 
200 pages, illustrated. Cloth, $1.25 net. 

Shaw on Nervous Diseases and Insanity 

Fourth Edition, Revised 

Essentials of Nervous Diseases and Insanity : their Symptoms and 
Treatment. A Manual for Students and Pra'ctitioners. By the late John 
C. Shaw, M. D., Clinical Professor of Diseases of the Mind and Nervous 
System, Long Island College Hospital, New York. i2mo of 204 pages, 
illustrated. Cloth, $1. 00 net. In Saunders' Question- Compend Series. 

Powell's Diseases of Children 3d Edition, Revised 

Essentials of the Diseases of Children. By William M. 
Powell, M. D. Revised by Alfred Hand, Jr., A. B., M. D., Dis- 
pensary Physician and Pathologist to the Children's Hospital, Philadel- 
phia. i2mo volume of 259 pages. Cloth, #1.00 net. In Saunders 1 
Question- Compend Series. 

Hecker, Trumpp, and Apt on Children 

A-llas and Epitome of Diseases of Children. By Dr. R. 
Hecker and Dr. J. Trumpp, of Munich. Edited, with additions, by 
Isaac A. Apt, M. D. With 48 colored plates, 144 text-cuts, and 453 
pages of text. Cloth, $5.00 net. 



SEP -0 !9M 



